WO2025226656A1

WO2025226656A1 - Hepatitis b virus mrna vaccines

Info

Publication number: WO2025226656A1
Application number: PCT/US2025/025733
Authority: WO
Inventors: Anthony T. DIPIAZZA; Yen-Ting Lai; Simone PECETTA; Yanbo Sun
Original assignee: ModernaTx Inc
Current assignee: ModernaTx Inc
Priority date: 2024-04-23
Filing date: 2025-04-22
Publication date: 2025-10-30
Anticipated expiration: 2026-10-23

Abstract

Provided herein are messenger ribonucleic acid vaccines for Hepatitis B virus infection and related methods of treatment.

Description

Attorney Docket No.45817-0192WO1 / MTX1067.20 HEPATITIS B VIRUS MRNA VACCINES CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority of U.S. Provisional Application No. 63/637,562, filed on April 23, 2024, and U.S. Provisional Application No.63/770,489, filed on March 12, 2025, the contents of which are incorporated by reference in their entirety herein. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on April 21, 2025, is named 45817-0192WO1_SL.xml and is 1,183,730 bytes in size. BACKGROUND Chronic HBV infection (CHB) is a significant global health burden, with over 290 million reported cases by WHO, despite effective prophylactic vaccination. Suppressive treatment with standard of care (SOC) nucleoside analogs (NUC) reduces risk of disease progression but is associated with very low functional cure rates. CHB is characterized by persistent latent reservoir with covalently closed circular DNA (cccDNA) and integrated genome in hepatocytes, which are sources of persistent serum HBsAg production - the main driver of immune exhaustion and tolerance. Recent advances in CHB clinical research suggest that combination of HBsAg suppression/interference (RNAi) and immune stimulation (IFNα) can break HBV- induced tolerance and achieve sustained serum HBsAg loss (marker of functional cure), although such functional cure rates are still low. As there is currently no effective treatment for CHB, novel immune stimulation approaches are necessary. 1 Attorney Docket No.45817-0192WO1 / MTX1067.20 SUMMARY CHB infection is a significant global burden, despite effective prophylactic vaccination. CHB is characterized by persistent latent viral reservoirs with covalently closed circular DNA (cccDNA) and integrated genomes in hepatocytes, which are sources of persistent serum HBsAg production, a main driver of immune exhaustion and tolerance. While suppressive treatment with SOC nucleoside analogs (NUCs) has reduced the risk of disease progression, it is associated with very low functional cure rates. Combination therapies of HBsAg suppression/interference (RNAi) and immune stimulation (IFNa) have been proposed for breaking HBV-induced tolerance, however, functional cure rates are still low. New immune stimulation approaches for advancing significant improvements, relative to such prior therapies, in the treatment of CHB are disclosed herein. It has been discovered that mRNA technology has the ability to overcome past therapeutic vaccine failures by eliciting robust Th1-skewed immunity against multiple antigen targets. A primary target of HBV vaccines has been the viral Envelope protein, composed of PreS1, PreS2 and Small domains. Multiple HBV Envelope antigens were designed and tested for immunogenicity as mRNA vaccines (i.e., membrane-bound, sub-viral particles (SVP), nanoparticles). As set forth herein, an immuno-focusing B-T cell approach to the PreS1S2 domain of HBV Envelope has been developed and shown to result in robust multi- functional immunity and potent HBV neutralization. These surprising results were achieved in spite of the presence of abundant viral decoys (non-infective serum HBsAg particles), which have been a limitation of prior HBsAg-focused vaccine approaches. Robust polyfunctional CD4+ and CD8+ T cell responses to Core protein (truncated mutant) and Polymerase protein (activity abolished mutant) were demonstrated. In addition, immunity to at least the three selected HBV antigens (PreS1S2, Core and Polymerase) was achieved with a multivalent mRNA formulation delivered in a lipid nanoparticle. 2 Attorney Docket No.45817-0192WO1 / MTX1067.20 The multivalent mRNA vaccine described herein resulted in (1) multifunctional IFN-y producing CD8 T cells with in vivo cytotoxic activity, (2) antibody-mediated ADCC, and (3) authentic virus neutralization in the presence of abundant viral decoys (non-infective serum HBsAg particles). This novel approach achieved viral clearance of infected hepatocytes via lytic and non-lytic mechanisms, suggesting that the cycles of infection-reinfection were blocked and represents a significant advance in the treatment of CHB. This robust immune stimulation of Th1 type cells will overcome limitations of previous and current vaccine candidates and the targeting of the reinfection cycle will prove more effective than targeting specific antigens for reduction or elimination. The mRNA formulation described herein can be used as a monotherapy or in combination with additional treatment modalities. In some embodiments, the combination therapy of the mRNA vaccines disclosed herein with inhibitors of viral replication is administered to a subject having CHB. Such replication inhibitors may include current standard of care therapies known in the art, e.g., nucleoside analogs (NUCs) and capsid assembly modulators. In some embodiments, the combination therapy is performed with known agents that reduce HBsAg. Such HBsAg reduction agents may include siRNA/ASOs or NAP/STOP. In some embodiments, combination therapy is performed with immune stimulators. Such immune stimulators may include art recognized TLR 7/8 agonists; checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1) and/or cytokines (e.g., IFN-g). In some aspects, the present disclosure described herein relates to a composition comprising a lipid nanoparticle and one or more messenger ribonucleic acids (mRNAs), wherein the one or more mRNAs comprise: a first open reading frame (ORF) comprising a nucleic acid sequence encoding a hepatitis B virus (HBV) envelope protein; a second ORF comprising a nucleic acid sequence encoding an HBV core protein; and a third ORF comprising a nucleic acid sequence encoding an HBV polymerase protein. In some embodiments, the HBV envelope protein includes a PreS1 domain and a PreS2 domain. 3 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the PreS1 domain and a PreS2 domain further include a lumazine synthase domain. In some embodiments, the HBV core protein includes a Core_149 protein. In some embodiments, the HBV polymerase protein includes a Polymerase8mut. In some embodiments, the composition further includes a fourth ORF including a nucleic acid sequence encoding a Small domain of HBV Envelope protein. In some embodiments, the composition includes three different mRNA molecules, wherein the first ORF is present in a first mRNA molecule, the second ORF is present in a second mRNA molecule, and the third ORF is present on a third mRNA molecule. In some embodiments, the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. In some embodiments, the HBV envelope antigen includes the amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. In some embodiments, the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 30-42. In some embodiments, the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:100. In some embodiments, the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence including a nucleic acid sequence of any one of SEQ ID Nos: 30- 42. In some embodiments, the first ORF further includes a nucleic acid sequence encoding a signal peptide. In some embodiments, the HBV core protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 4 Attorney Docket No.45817-0192WO1 / MTX1067.20 97%, at least 98%, at least 99% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. In some embodiments, the HBV core protein includes the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. In some embodiments, the HBV core protein includes SEQ ID NO:2, SEQ ID NO:28, or a protein that differs from SEQ ID NO:2 or SEQ ID NO:28 by 1-10 amino acids. In some embodiments, the HBV core protein is SEQ ID NO:2 or SEQ ID NO:28. In some embodiments, the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 43, 44 or 46. In some embodiments, the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:104. In some embodiments, the ORF encoding the HBV core protein includes a nucleic acid sequence including a nucleic acid sequence of any one of SEQ ID Nos:43, 44 or 46 In some embodiments, the HBV polymerase protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1 or 29. In some embodiments, the HBV polymerase protein comprises a protein that differs from SEQ ID NOs: 1 or 29 by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids. In some embodiments, the different amino acids are present in a terminal protein domain, a spacer domain, a reverse transcriptase domain, and/or a RNase H domain of the HBV polymerase protein. In some embodiments, the HBV polymerase protein is SEQ ID NOs: 1 or 29. In some embodiments, the ORF encoding the HBV core protein comprises nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 5 Attorney Docket No.45817-0192WO1 / MTX1067.20 96%, at least 97%, at least 98%, at least 99% or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 47 or 48. In some embodiments, the ORF encoding the HBV core protein comprises nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:109. In some embodiments, the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos:47 or 48. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:24; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:28; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:29. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:24, wherein the first ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:100; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:28, wherein the second ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:104; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:29, wherein the third ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:109. 6 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:28; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:29. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24, wherein the first ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:100; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:28, wherein the second ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:104; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:29, wherein the third ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:109. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino 7 Attorney Docket No.45817-0192WO1 / MTX1067.20 acid sequence set forth in SEQ ID NO:24, wherein the first ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:100; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28, wherein the second ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:104; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29, wherein the third ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO:109. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24, wherein the first mRNA comprises the sequence set forth in SEQ ID NO:99; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28, wherein the second mRNA comprises the sequence set forth in SEQ ID NO:103; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29, wherein the third mRNA comprises the sequence set forth in SEQ ID NO:108. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24, wherein the first mRNA comprises the sequence set forth in SEQ ID NO:412; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28, wherein the second mRNA comprises the sequence set forth in SEQ ID NO:413; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29, wherein the third mRNA comprises the sequence set forth in SEQ ID NO:414. 8 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the mRNA comprises a chemical modification. In some embodiments, the lipid nanoparticle comprises an ionizable lipid, a neutral lipid, a sterol, and a PEG-modified lipid. In some embodiments, the lipid nanoparticle comprises 40-55 mol% of the ionizable lipid, 30-45 mol% of the sterol, 5-15 mol% of the neutral lipid, and 1-5 mol% of the PEG-modified lipid. In some embodiments, the ionizable lipid is a lipid of Formula (IL*): or a salt thereof, wherein: R¹ is -OH, -NR^N-C4-10 cycloalkenyl optionally substituted with one or more oxo or -N(R^N’R^N’’); R^N is H or C1-6 alkyl; R^N’ is H or C1-6 alkyl; R^N’’ is H or C_1-6 alkyl; o is 1, 2, 3, or 4; n is 4, 5, 6, 7, or 8; m is 4, 5, 6, 7, or 8; M is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R²; M’ is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R³; R² or –(C_1-6 alkylene)-(C_3-8 cycloalkyl)-C_1-6 alkyl; R^2a R^2b is -H or C1-10 alkyl; R^2c is C_1-8 alkyl or C_2-8 alkenyl; 9 Attorney Docket No.45817-0192WO1 / MTX1067.20 ; 8 and R^3c is C1-10 alkyl or C2-8 alkenyl. In some embodiments, the ionizable lipid is Compound (I-25) . ; 3-phosphocholine (DSPC); the sterol is cholesterol; and the PEG-modified lipid is PEG2000-DMG. In some aspects, the disclosure relates to a method of treating HBV disease in a human subject in need thereof by administering to the human subject one or more doses of a composition described herein in an effective amount to produce an immune response to an HBV. In some aspects, the disclosure relates to a method, comprising administering a single dose of the composition to the subject or administering a prime dose and at least one booster dose of the vaccine to the subject. In some embodiments, the HBV disease is chronic HBV disease. In some aspects, the disclosure relates to a method of treating chronic HBV disease in a subject in need thereof, the method comprising administering to the subject one or more doses of a trivalent mRNA vaccine encoding a hepatitis B virus (HBV) envelope protein, a HBV core protein, and a HBV polymerase protein. 10 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the methods described herein, the HBV envelope protein comprises a PreS1 domain and a PreS2 domain, optionally linked to a lumazine synthase domain, the HBV core protein includes a Core_149 protein and, and the HBV polymerase protein includes a Polymerase8mut. In some embodiments of the methods described herein, the trivalent mRNA vaccine is sufficient to produce sustained undetectable HBsAg and HBV DNA in a treated subject. In some embodiments of the methods described herein, the trivalent mRNA vaccine is sufficient to produce HBsAg seroconversion in a treated subject. In some embodiments of the methods described herein, the trivalent mRNA vaccine is sufficient to produce a functional cure in in a treated subject. In some embodiments of the methods described herein, the trivalent mRNA vaccine comprises a composition including a lipid nanoparticle and one or more mRNAs, wherein the one or more mRNAs comprise at least a first open reading frame (ORF) comprising a nucleic acid sequence encoding the HBV envelope protein, a second ORF comprising a nucleic acid sequence encoding the HBV core protein, and a third ORF comprising a nucleic acid sequence encoding the HBV polymerase protein. In some embodiments of the methods described herein, the trivalent mRNA vaccine comprises at least three different mRNAs, and wherein the first ORF is present in a first mRNA, the second ORF is present in a second mRNA, and the third ORF is present in a third mRNA. In some embodiments of the methods described herein, the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. In some embodiments of the methods described herein, the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD4+ cell activity against HBV. 11 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the methods described herein, the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD8+ cell activity against HBV. In some embodiments of the methods described herein, the method further comprises administering PEG-IFN monotherapy and/or Nucleos(t)ide analogues (NUCs) to the subject. In some embodiments of the methods described herein, the method further comprises administering siRNA to the subject. In some embodiments of the methods described herein, the method further comprises administering antisense oligonucleotides (ASOs) to the subject. In some embodiments of the methods described herein, the method further comprises administering PEG-IFN monotherapy and/or nucleos(t)ide analogues (NUCs) to the human subject prior to initiation of treatment with the composition. In some embodiments, the PEG-IFN monotherapy and/or the NUCs are administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. In some embodiments of the methods described herein, the method further comprises administering an siRNA that targets HBV to the human subject prior to initiation of treatment with the composition. In some embodiments, the siRNA that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. In some embodiments of the methods described herein, the method further comprises administering an antisense oligonucleotide that targets HBV to the human subject prior to initiation of treatment with the composition. In some embodiments, the antisense oligonucleotide that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. 12 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the methods described herein, the method further comprises administering to the human subject at least one immunostimulatory antibody or at least one mRNA encoding at least one immunostimulatory antibody. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-OX40 antibody. In some embodiments, the agonist anti-OX40 antibody is tavolimab, MOXR-0916, PF-04518600, GSK3174998, BMS-986178, INCAGN01949, or 9B12. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-CD27 antibody. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-4-1BB (also known as CD137) antibody. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-GITR antibody. In some embodiments, the at least one immunostimulatory antibody is an antagonist of an immune checkpoint molecule. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-PD-1antibody. In some embodiments, the antagonist anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, sintilimab, retifanlimab, AB122, AMP-224, JTX-4014, BGB-108, BCD-100, BAT1306, LZM009, AK105, HLX10, or TSR-042. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-PD-L1 antibody. In some embodiments, the antagonist anti-PD-L1 antibody is atezolizumab, avelumab, durvalumab, tislelizumab, BMS-935559, MEDI4736, FAZ053, KN035, CS1001, SHR-1316, CBT-502, A167, STI-A101, CK-301, BGB-A333, MSB-2311, HLX20, or LY3300054. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-CTLA-4 antibody. In some embodiments, the antagonist anti-CTLA-4 antibody is ipilimumab, tremelimumab, AGEN1884, or CP-675,206. 13 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-LAG-3 antibody. In some embodiments, the antagonist anti-LAG-3 antibody is relatlimab, LAG525, or INCAGN2385. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-PD-L2 antibody. In some aspects, the present disclosure described herein relates to a composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a protein including an amino acid sequence that is SEQ ID NOs: 1-7, 16-26, or 28-29. In some aspects, the present disclosure described herein relates to an HBV antigen comprising an amino acid sequence including at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1-7, 16-26, or 28-29. In one embodiment, the mRNA composition comprises a quadrivalent formulation including a fourth antigen, the Small domain of HBV Envelope. The quadrivalent formulation elicited specific antibodies and Th1-skewed T cell responses against all antigens. Inclusion of the Small antigen provides a potential benefit for patients receiving combination therapy (including NUCs and siRNA/ASO), that may result in reduced expression of PreS1S2 antigens by the infected hepatocytes. In contrast the Small antigen is constitutively expressed by integrated HBV DNA in the host cell. BRIEF DESCRIPTION OF THE DRAWINGS FIGs.1A-1E are graphs depicting the results of studies involving mice administered mRNA encoding HBV envelope antigens (Genotype A), as described in Table 3, to test the immunogenicity of the vaccine. Antigen specific IgG titers from vaccinated mice directed towards PreS1, PreS1/S2, and small HBV envelope antigens are shown in FIGs.1A, 1B, and 1C, respectively. Levels of 50% neutralizing titer (NT50) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope antigens are shown in FIG.1D. The percent (%) signal reduction 14 Attorney Docket No.45817-0192WO1 / MTX1067.20 measured by a competition ELISA assay and correlation with antigen specific IgG titers directed towards PreS1 or NT₅₀ are shown in FIGs.1E. FIGs.2A-2B are graphs depicting cell-mediated responses of spleen cells obtained from mice immunized with HBV polymerase protein constructs in Table 4. CD4+ T cell responses after stimulation by CD4+ (15-mer) are shown in FIG.2A. CD8+ T cell responses after stimulation by CD8+ (15-mer) are shown in FIG.2B. The y-axis shows the percentage (%) of cells that have a marker selected from, CD107a, IFN-γ, TNF-α, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). FIGs.3A-3B are graphs depicting intracellular cytokine staining of splenocytes obtained from mice immunized with polymerase protein constructs in Table 5. CD4+ T cell responses after stimulation by CD4+ (core peptide pool) are shown in FIG.3A. CD8+ T cell responses after stimulation by CD8+ (core peptide pool) are shown in FIG. 3B. The y-axis shows the percentage (%) of cells that have a marker selected from, CD107a, IFN-γ, TNF-α, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). FIGs.4A-4H are graphs depicting the results of studies involving mice administered multivalent mRNA formulations encoding a combination of HBV envelope (Genotype A), polymerase (Genotype D), and core antigens (Genotype D), as described in Table 6, to test the immunogenicity of the vaccine. Total HBV specific IgG titers directed towards PreS1/S2 are shown in FIG.4A, with day 22 and day 43 time points in red and blue, respectively. Levels of 50% neutralizing titer (NT₅₀) depicting vaccine- induced humoral immunity after the vaccination against HBV with HBV envelope, polymerase, and core antigens are shown in FIG.4B. CD8+ T cell responses after stimulation by CD8+ preS1/S2 peptide pool, core peptide pool, and polymerase peptide pool are shown in FIGs.4C, 4D, and 4E, respectively. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-γ, TNF- α, or IL-2. CD4+ T cell responses after stimulation by CD4+ preS1/S2 peptide pool, core 15 Attorney Docket No.45817-0192WO1 / MTX1067.20 peptide pool, and polymerase peptide pool is shown in FIGs.4F, 4G, and 4H, respectively. The y-axis shows the percentage (%) of CD4+ T cells that have a marker selected from, IFN-γ, TNF-α, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). FIGs.5A-5O are graphs depicting the results of studies involving mice administered mRNA encoding HBV envelope antigens (Genotype A), as described in Table 7, to test the durability of the vaccine. Total HBV specific IgG titers directed towards PreS1/S2, or small envelope antigen were measured. Levels of 50% neutralizing titer (NT₅₀) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope antigens are shown in FIG.5A. CD8+ T cell responses after stimulation by CD8+ preS1/S2 peptide pool, large peptide pool, or small peptide pool are shown in FIGs.5B-5C, 5F-5G, and 5K-5L, respectively. The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-γ, TNF-α, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). CD4+ T cell responses after stimulation by CD4+ preS1/S2 peptide pool, large peptide pool, or small peptide pool are shown in FIGs.5D-5E, 5H-5I, and 5M-5N, respectively. The y-axis shows the percentage (%) of CD4+ T cells that have a marker selected from, IFN-γ, TNF-α, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). Plasma cells directed to small and PreS1/S2 or PreS1 are shown in FIGs.5O, and 5J, respectively. FIGs.6A-6C are graphs depicting the results of studies involving mice administered mRNA encoding a combination of HBV envelope (Genotype A) and HBV core (Genotype D) antigen variants, as described in Table 8, to test the immunogenicity of the vaccine. Total HBV specific IgG titers directed towards PreS1, or core antigens were measured. Levels of 50% neutralizing titer (NT50) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope and core antigens are shown in FIG.6A. CD8+ T cell responses after stimulation by CD8+ preS1/S2 peptide pool, or core peptide pool are shown in FIG.6B. The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-γ, TNF- 16 Attorney Docket No.45817-0192WO1 / MTX1067.20 α, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). CD4+ T cell responses after stimulation by CD4+ preS1/S2 peptide pool, or core peptide pool are shown in FIG.6C. The y-axis shows the percentage (%) of CD4+ T cells that have a marker selected from, IFN-γ, TNF-α, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). FIGs.7A-7D are graphs depicting the results of studies involving mice administered mRNA encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes, as indicated in Table 9, to test the immunogenicity of alternative HBV genotypes. Levels of 50% neutralizing titer (NT₅₀) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope, core, and polymerase proteins are shown in FIG.7A. CD8+ and CD4+ T cell responses after stimulation by preS1/S2 peptide pool, core peptide pool, and polymerase peptide pool are shown in FIGs.7B, 7C, and 7D, respectively. The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-γ, TNF-α, or IL-2 or the percentage (%) of CD4+ T cells that have a marker selected from, IFN-γ, TNF-α, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (µg mRNA). FIG 8 is a bar graph depicting the results of a study in mice administered a trivalent mRNA vaccine encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes and measuring CTL-specific killing. Briefly, antigen presenting cells were pulsed with PreS1 (HBV Genotype A), Core (HBV Genotype D), Pol (HBV Genotype D) Peptides and IV dosed in vaccinated mice; after 16 hours percent (%) killing was calculated in relation to PBS-treated mice. FIGs.9A-9D are graphs depicting the results of studies involving mice administered a quadrivalent mRNA vaccine encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes demonstrating that antigens are immunogenic in quadrivalent combination. FIG.9A shows that a quadrivalent vaccine induced comparable anti-PreS1/S2 IgG titer and lower anti-Small 17 Attorney Docket No.45817-0192WO1 / MTX1067.20 IgG compared to the respective monovalent vaccine. FIG.9B shows that a quadrivalent vaccine induced lower live virus neutralization as compared to Small monovalent vaccine, but higher neutralization compared to PreS1S2_LuS vaccine alone. FIG.9C shows that antibody induced by quadrivalent vaccine displayed enhanced antibody- dependent cellular cytotoxicity (ADCC) as compared to PreS1S2 monovalent vaccine. FIGs.9D shows that a quadrivalent vaccine elicited robust, yet slightly decreased, CD8+ and CD4+ (Th1-dominated) T cells to all four antigens as compared to monovalent vaccines. FIG.10 is a graph depicting PreS1S2-binding antibodies in Cynomolgus macaque serum after immunization with the trivalent mRNA vaccine. Serum samples were collected on Days -7, 14, 42, and 70, and IgG binding titers against the HBV PreS1S2 antigen (genotypes A, B, C, and D, as identified in the panel titles) were measured by ELISA. Each dot represents an individual macaque, with the line and error margins representing the geometric mean with 95% confidence intervals. The y-axis represents the antibody titers specific to PreS1S2 of the respective genotype, with the lower limit of detection (LLOD) indicated by the dashed line. FIG.11 is a graph depicting live HBV (genotype D) neutralization in Cynomolgus macaque serum after immunization with the trivalent mRNA vaccine. Serum samples were collected on Days -7, 14, 42, and 70, and neutralization titer (NT50) of HBV in vitro infectivity was measured. Each dot represents an individual macaque, with the line and error margins represent the geometric mean with 95% confidence intervals. The y-axis represents the NT50 neutralization titer, with LLOD indicated by the dashed line. FIG.12 contains graphs depicting CD8+ T cell responses (top panel) and CD4+ T cell responses (bottom panel) after immunization with the trivalent mRNA vaccine. Splenocytes were collected on Day 70 and HBV antigen specific CD8+ T cell and CD4+ T cell responses were measured by intracellular cytokine staining. The bar heights and error margins represent the geometric mean with 95% confidence intervals. Y axis indicates the percentage of the CD8+ T cell or CD4+ T cell population expressing the 18 Attorney Docket No.45817-0192WO1 / MTX1067.20 evaluated CD8+ or CD4+ cytokines in combination with CD69+, with the assay LLOD defined by the dashed line. FIG.13A is a graph depicting serum HBsAg levels over time in mice with differing starting levels of HBV viremia (1×10^10, 5×10^9, 1×10^9, or 5×10^8 of AAV- HBV viral genome administered) following treatment with the trivalent mRNA vaccine (HBV Tx) or PBS. HBV Tx and PBS treatments were administered on Day 0, Day 14, Day 28, and Day 42 (indicated as Vx in the graph). FIG.13B is a graph depicting serum HBeAg levels over time in mice with differing starting levels of HBV viremia (1×10^10, 5×10^9, 1×10^9, or 5×10^8 of AAV- HBV viral genome administered) following treatment with the trivalent mRNA vaccine (HBV Tx) or PBS. HBV Tx and PBS treatments were administered on Day 0, Day 14, Day 28, and Day 42 (indicated as Vx in the graph). FIG.14 is a graph depicting the percentage of HBV core antigen-positive cells out of total liver cells in HBV Tx-treated mice or PBS-treated mice in each AAV-HBV dose group (1×10^10, 5×10^9, 1×10^9, or 5×10^8 of AAV-HBV viral genome administered). FIG.15 is a graph depicting serum HBsAg levels, serum HBeAg levels, and serum HBV DNA levels over time in mice with differing starting levels of HBV viremia (1×10^10 or 5×10^9 of AAV-HBV viral genome administered) following treatment with the trivalent mRNA vaccine (HBV Tx), the trivalent mRNA vaccine in combination with an agonistic anti-OX40 antibody and an antagonistic anti-PD-L1 antibody (HBV Tx + aOX40/PD-L1), or PBS. HBV Tx and PBS treatments were administered on Day 0, Day 14, Day 28, and Day 42 (indicated as Vx in the graph). aOX40/PD-L1 treatments were administered on Day 49, Day 52, Day 55, Day 58, and Day 61. FIG.16 is a graph depicting the percentage of HBV core antigen-positive cells out of total liver cells in HBV Tx-treated mice, HBV Tx + aOX40/PD-L1-treated mice, or PBS-treated mice in each AAV-HBV dose group (1×10^10, 5×10^9, 1×10^9, or 5×10^8 of AAV-HBV viral genome administered). 19 Attorney Docket No.45817-0192WO1 / MTX1067.20 DETAILED DESCRIPTION Developing vaccines for chronic Hepatitis B Virus (HBV) has been a significant challenge due to a variety of complex factors. For example, HBV infection produces excess subviral particles (SVPs) that may act as decoys to escape virus neutralization. Also, patients with chronic HBV infections usually have T cells which are exhausted owing to chronic stimulation leading to weak virus-specific T-cell responses and killing, leading to reduced clearance of virus and recovery from hepatitis. In addition to CD4+ and CD8+ T cells with reduced function, HBV-mediated immune exhaustion is associated with dysfunctional HBS envelope antigen (HBsAg)-specific memory B cells responses. Management of chronic hepatitis B disease involves breaking immune tolerance and eliciting durable, protective immunity. An additional challenge to creating a vaccine effective across different populations is that the prevalent HBV Genotype differs by region. In Asia Pacific, Genotypes B and C are most prevalent. In Europe, Genotypes A and D are most prevalent. In Central/South America Genotypes H and/or F are most prevalent. In Africa, Genotype E is most prevalent. In North America, genotype A is most prevalent. Despite greater than 80% global coverage of highly effective prophylactic vaccination in infants, the World Health Organization estimates over 290 million people are living with chronic HBV. Although current therapeutic HBV therapies (including vaccines) have been found to be relatively safe for chronic HBV patients, they have not been shown to achieve sustained rates of cure in this population. The majority of acute infections by the highly transmissible HBV are cleared spontaneously. Progression to chronic HBV (CHB) is age dependent. Untreated chronic HBV can progress to cirrhosis, liver failure, and/or hepatocellular carcinoma. Both PEG- IFN monotherapy and Nucleos(t)ide analogues (NUCs) are recommended as first-line therapies in treatment-naïve chronic HBV patients. Despite these standard of care treatments, the global burden of CHB disease is immense and even incremental improvements in functional cure rate will be of high clinical value. 20 Attorney Docket No.45817-0192WO1 / MTX1067.20 The vaccine compositions and methods of the present disclosure overcome one or more of the foregoing challenges. In one aspect, they increase CD4+ cell activity against HBV, as compared to limited CD4+ immune response in CHB that occurs because of immune exhaustion and/or tolerance. In another aspect, they increase CD8+ cell activity against HBV, as compared to limited CD8+ immune response in CHB that occurs because of immune exhaustion and/or tolerance. In another aspect, they increase B cell activity against HBV, as compared to limited B immune response in CHB that occurs because of immune exhaustion and/or tolerance. In another aspect, vaccine compositions and methods of the present disclosure are useful for treating a patient chronically infected with HBV, who has had an HBV infection that lasts more than six months (chronic infection, CHB), by inducing a functional cure of CHB. A “functional cure” of CHB in a subject is associated with reaching certain clinical markers. In some embodiments, a functional cure in a subject is defined as near undetectable HBV DNA in serum of the subject and near undetectable levels of hepatitis B surface antigen (HBsAg), with or without achieving anti-HBs seroconversion, elimination of detectable HBV RNA, and/or HBcrAg, using standard clinical measurements. Near undetectable HBsAg, in some embodiments refers to ≤100 IU/mL HBsAg in serum. Nearly undetectable HBV DNA, in some embodiments refers to ≤20 IU/mL HBV DNA in serum. In some embodiments the functional cure is determined after a defined time period of treatment. In some embodiments a functional cure is determined at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, or at least 11 months following treatment with the vaccine compositions of the disclosure. In some embodiments a functional cure is determined 3-6 months, 4-6 months, 5-6 months, 6-12 months, 7-12 months, 8-12 months, 9-12 months, 10-12 months, or 11-12 months following treatment with the vaccine compositions of the disclosure. In some embodiments a functional cure is determined 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months, or 1, 2, 3, 4, or 5 years following treatment with the vaccine compositions of the disclosure. In one embodiment, functional cure of CHB is measured in the absence of NUC treatment. 21 Attorney Docket No.45817-0192WO1 / MTX1067.20 In an embodiment, the instant vaccine improves the rate of functional cure as compared to NUC treatment (with or without IFNg) thereby allowing patients to forgo lifelong treatment with NUC. In some embodiments before achieving functional cure, the vaccine compositions and methods of the disclosure result in a favorable HBsAg response (FHR). A FHR is defined as HBsAg seroclearance or HBsAg ≤100 IU/mL at a time period following initiation of treatment. In another aspect, the vaccine compositions and methods of the present disclosure treat a patient chronically infected with HBV by generating functional T cell and B cell immunity in the patient. In another aspect the vaccine compositions and methods establish functional immunity in a patient chronically infected with HBV. In another aspect the vaccine compositions and methods achieves any one or all of the foregoing advantages across multiple genotypes. Hepatitis B Virus Proteins The Hepatitis B Virus (HBV), a member of the Hepadnaviridae family, includes a relaxed, circular, partially double stranded DNA genome that uses an RNA intermediate, pregenomic RNA (pgRNA), and reverse transcriptase for its genome replication. HBV produces 3 different types of virus-related particles as follows i) spherical, double shelled particles, 42–47 nm in diameter, ii) spherical particles, 17-22 nm in diameter, and iii) filaments 20 nm in diameter and of variable length. The 42–47 nm double shelled particles, called Dane particles, are the infectious particles. HBV DNA codes for Envelope (HBsAg), Core (HbcAg), and E (HbeAg), X protein HBx) and Polymerase (Pol). HBV enters hepatocytes by low-affinity binding to heparan sulfate proteoglycans and subsequent high-affinity interaction with sodium taurocholate co-transporting polypeptide (NTCP) receptors. Once internalized, circular viral DNA (rcDNA) is processed by cellular enzymes to stable minichromosomes of covalently closed circular DNA (cccDNA). Linear dsDNA is produced as a result of infection and integrated into the genome. Pregenomic RNA (pgRNA) is reverse 22 Attorney Docket No.45817-0192WO1 / MTX1067.20 transcribed by HBV Pol inside nascent nucleocapsids and the resultant gapped circular dsDNA is encapsidated into new infectious viral particles. The vaccine compositions of the disclosure are mRNA vaccines encoding HBV antigens. As an aspect of the present disclosure is it has been discovered that mRNA vaccines encoding HBV antigens, such as three or four different antigens are useful and effective for treating a patient chronically infected with HBV, and in some embodiments producing a functional cure. In some embodiments the mRNA vaccines encode an HBV envelope antigen, an HBV polymerase antigen and a core antigen. HBV Viral polymerase (Pol) In some embodiments, an HBV protein encoded by an mRNA of the present disclosure comprises an HBV polymerase protein. In some embodiments the HBV polymerase protein comprises a Pol-8mut (D). As described herein, the term, “HBV polymerase protein” refers to a wild-type HBV Viral polymerase (Pol) or a variant thereof. In some embodiments, an HBV polymerase protein “variant thereof” is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% identical to SEQ ID NO: 1. In some embodiments, the HBV polymerase protein is an HBV genotype A, B, C, D, E, F, G, or H. The HBV polymerase is encoded by Gene P and has four domains with three enzymatic activities. Pol is the central enzyme in genome replication. The four domains are: (1) a terminal protein (TP) domain with protein-priming function; (2) a non-conserved spacer domain with no enzymatic activity; (3) a reverse transcriptase (RT) domain with RNA-dependent DNA polymerase (RT) and DNA-dependent DNA polymerase activity; and (4) a RNase H domain with ribonuclease H activity. In some embodiments, the polymerase protein comprises a wild-type polymerase protein, or a variant thereof. In some embodiments, the wild-type polymerase protein is from HBV genotype D. In some embodiments, the wild-type polymerase protein is encoded by the amino acid sequence of: MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSI PWTHKVGNFTGLYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTV 23 Attorney Docket No.45817-0192WO1 / MTX1067.20 NEKRRLQLIMPARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTL WKAGILYKRETTHSASFCGSPYSWEQELQHGAESFHQQSSGILSRPPVGSS LQSKHSKSRLGLQSQQGHLARRQQGRSWSIRAGIHPTARRPFGVEPSGSG HNTNLASKSASCLYQSPLRKAAYPAVSTFEKHSSSGHAVELHNLPPNSAR SQGERPVFPCWWLQFRNSKPCSDYCLSHIVNLLEDWGPCAEHGEHHIRIP RTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGNYRVSWPKFAVPNL QSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYVARLS SNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFR KIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHL ESLFTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQK IKECFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQ AFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLVMGHQ RMRGTFLAPLPIHTAELLAACFARSRSGANILGTDNSVVLSRKYTSFPWLL GCAANWILRGTSFVYVPSALNPADDPSRGRLGLSRPLLRLPFRPTTGRTSL YADSPSVPSHLPDRVHFASPLHVAWRPP (SEQ ID NO: 1) In some embodiments, the polymerase protein comprises a polymerase protein variant that comprises one or more mutations relative to a naturally occurring HBV polymerase protein. The terms “naturally occurring” and “wild type” are used interchangeably herein to refer to a protein sequence that is comprised of the same type of amino acids found in a protein that is present in nature. A naturally occurring HBV polymerase protein is an HBV polymerase protein that comprises an amino acid sequence that is the same as an amino acid sequence of an HBV polymerase protein that occurs in nature, i.e., which is a naturally occurring isolate. A naturally occurring protein is not genetically (or otherwise) modified to substitute, remove, or add any amino acids relative to the protein found in nature. However, a naturally occurring or wild type protein may be produced by recombinant technology or other synthetic techniques. In some embodiments, the polymerase protein comprises at least one mutation(s) relative to the wild-type polymerase protein encoded by SEQ ID NO: 1. In some embodiments, the polymerase protein comprises at least one mutation(s) and not more than 10 mutations relative to the wild-type polymerase protein encoded by SEQ ID NO: 1. In some embodiments, the polymerase protein comprises 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more mutation(s) relative to the wild-type polymerase protein encoded by SEQ ID NO: 1. 24 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the polymerase protein comprises a Pol-8mut (D), which comprises at least 1, 2, 3, 4, 5, 6, 7 or 8 amino acid mutation(s) at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 63. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a valine (V) at amino acid position 63. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A) at amino acid position 63. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 312. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 312. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 312. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 312. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 323. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 323. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 323. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 323. 25 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 327. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 327. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 327. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 327. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 341. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 341. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 341. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 341. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 703. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, an arginine (R) at amino acid position 703. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 703. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, 26 Attorney Docket No.45817-0192WO1 / MTX1067.20 an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 703. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 777. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, an aspartic acid (D) at amino acid position 777. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 777. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 777. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 781. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, an arginine (R) at amino acid position 781. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 781. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 781. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 are present in the TP domain, Spacer domain and/or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and/or Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and/or RNAseH domain. In some 27 Attorney Docket No.45817-0192WO1 / MTX1067.20 embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain and/or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain, Spacer domain and RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain and RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain, Spacer domain or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain or Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the RNAseH domain. In some embodiments, the at least one, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 mutations are present in the polymerase protein. In some 28 Attorney Docket No.45817-0192WO1 / MTX1067.20 embodiments the mutations are selected from Y63A, C312A, C323A, C327A, C341A, R703A, D777A, and R781A. In some embodiments the polymerase protein comprises any combination of one or more of such mutations, such as those depicted in Table 12. In Table 12 an “X” is used to denote the presence of an amino acid mutation at the indicated amino acid position. Table 12: HBV polymerase protein mutant described herein. No. SEQ ID NO: Amino acid position I-1 111 Y63A Attorney Docket No.45817-0192WO1 / MTX1067.20 I-21 130 Y63A-C341A I-22 131 Y63A-C341A-R703A Attorney Docket No.45817-0192WO1 / MTX1067.20 II-5 158 C312A-C323A-C327A-C341A-R703A II-6 159 C312A-C323A-C327A-C341A-R703A-D777A Attorney Docket No.45817-0192WO1 / MTX1067.20 III-11 186 Y63A-C323A-C341A-R703A-D777A-R781A III-12 187 C323A-R703A Attorney Docket No.45817-0192WO1 / MTX1067.20 V-1 214 C341A V-2 215 Y63A-C312A-C341A Attorney Docket No.45817-0192WO1 / MTX1067.20 VI-12 242 Y63A-C312A-R703A-R781A VI-13 243 Y63A-C312A-C323A-R703A-R781A Attorney Docket No.45817-0192WO1 / MTX1067.20 IX-4 269 C323A-R703A-R781A IX-5 270 C323A-C341A-R781A No. SEQ ID NO: Amino acid position Attorney Docket No.45817-0192WO1 / MTX1067.20 IX-31 296 C312A-C323A-R703A-R781A IX-32 297 C312A-C323A-R703A-D777A Attorney Docket No.45817-0192WO1 / MTX1067.20 IX-59 324 Y63A-C323A-R703A-D777A IX-60 325 Y63A-C323A-C341A Attorney Docket No.45817-0192WO1 / MTX1067.20 IX-87 352 Y63A-C312A-C327A-C341A IX-88 353 Y63A-C312A-C327A-C341A-R781A Core ant gen As described herein, the term, “HBV core protein” refers to a wild-type HBV core protein (HBc and HBe antigens) or a variant thereof. In some embodiments, an HBV core protein “variant thereof” is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% identical to SEQ ID NO: 2. In some embodiments, the HBV core protein is an HBV genotype A, B, C, D, E, F, G, or H. The HBV core proteins are encoded by Gene C. The core genes encode the structural protein of the nucleocapsids as well as the ‘e’ antigen (HBeAg). The HBc antigen is an icosahedral nucleocapsid and the HBe antigen has immunoregulatory roles. The core protein is a 183 amino acid residue protein that self-assembles to form the viral capsid. In an infected cell core modulates almost every step of the viral lifecycle. Core participates in regulation of reverse transcription and signals completion of reverse transcription to support virus secretion. Core carries both nuclear localization signals and HBV envelope antigen (HBsAg) binding sites. The assembly domain of the HBV core protein is amino acid residues 1- 149. 38 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, an HBV protein encoded by an mRNA of the present disclosure comprises an HBV core protein (alone or in multimeric form as disclosed herein). In some embodiments, the core protein comprises a wild-type core protein, or a variant thereof. In some embodiments, the wild-type core protein is from HBV genotype D. In some embodiments, the wild-type core protein is encoded by the amino acid sequence of: MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPH HTALRQAILCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQ LLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRR RGRSPRRRRTPSPRRRRSQSPRRRRSQSRESQC (SEQ ID NO: 2) In some embodiments, the core protein comprises a C-terminal truncation relative to a wild-type core protein amino acid sequence. In some embodiments, the core protein comprises a C-terminal truncation relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acids 1- 149 relative to a wild-type core protein (e.g., SEQ ID NO: 2). In some embodiments, the core protein comprises a C-terminal truncation of about 35 (e.g., 20, 25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45) amino acids relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the core protein comprises a C-terminal truncation of about 20, 25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45 amino acids relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the core protein comprises a C-terminal truncation of about 35 amino acids relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acid positions about 1-149 (1-200, 1-150, 1-149, 1-140, 1-123, 1-100, 1-50, 10-200, 10- 150, 10-149, 10-140, 10-123, 10-100, 10-50, 25-200, 25-150, 25-149, 25-140, 25-123, 25-250, 25-50) relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acid positions about 1-200, 1-150, 1-149, 1-140, 1-123, 1-100, 1-50, 10-200, 10-150, 10-149, 10-140, 10-123, 10-100, 10-50, 25-200, 25-150, 25-149, 25-140, 25-123, 25-250, 25-50 relative 39 Attorney Docket No.45817-0192WO1 / MTX1067.20 to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acid positions about 1-149 relative to the amino acid sequence of SEQ ID NO: 2. HBV Envelope antigen As described herein, the term, “HBV envelope antigen” refers to the HBV envelope antigen or variants thereof. In some embodiments, an “HBV envelope antigen variant thereof” is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% identical to any one of SEQ ID NOs: 3-7, or 49. In some embodiments, the HBV envelope antigen is an HBV genotype A, B, C, D, E, F, G, or H. The HBV envelope antigens are encoded by Gene S. The Gene S region encodes three different envelope glycoproteins, small (SHBs), middle (MHBs), and large (LHBs). The small, middle, and large envelope antigen share a common C-terminal. The N-terminal portion of the large envelope antigen is the PreS1 domain. The N-terminal portion of the middle envelope antigen is the PreS2 domain. The large envelope antigen is approximately 400 amino acids in length. The middle envelope antigen is approximately 281 amino acids in length. The small envelope antigen is approximately 226 amino acids in length. The large, middle, and small envelope antigen protein share a common C terminus. In some embodiments the mRNA encodes the HBV envelope antigen or variants thereof (alone or in multimeric form as disclosed herein). In each of the descriptions of fusion proteins presented herein the proteins are listed in N-terminal to C-terminal orientation. The N-terminal of the large envelope antigen is the PreS1 domain. The PreS1 domain extends from amino acid position 1 to 119 of the large envelope antigen. The PreS1 domain contains functional sites, B-cell epitopes, and T-cell epitopes. The N-terminal of the middle envelope antigen is the PreS2 domain. The PreS2 domain extends from amino acid 120 to 174 of the large envelope antigen. The PreS2 domain contains functional sites, B-cell epitopes, and T-cell epitopes. In some embodiments, an HBV protein encoded by an mRNA of the present disclosure comprises an HBV envelope antigen. 40 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the envelope antigen comprises a small envelope antigen or a variant thereof. In some embodiments, the envelope antigen comprises a PreS1/S2 or variants thereof. In some embodiments, the envelope antigen comprises a small envelope antigen variant that comprises one or more mutations relative to a naturally occurring HBV small envelope antigen. In some embodiments, the PreS1/S2 antigen comprises a PreS1/S2 variant that comprises one or more mutations relative to a naturally occurring HBV PreS1/S2 protein. In some embodiments, the envelope antigen comprises a wild-type envelope antigen, or a variant thereof. In some embodiments, the wild-type envelope antigen is from HBV genotype A. In some embodiments, the wild-type envelope antigen is a wild-type HBV small envelope antigen encoded by the amino acid sequence of: MENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQ NSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGML PVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSW AFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGP SLYSIVSPFIPLLPIFFCLWVYI (SEQ ID NO: 3) In some embodiments, the wild-type envelope antigen is a wild-type HBV middle envelope antigen encoded by the amino acid sequence of: MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTG DPVTNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSP VCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLD YQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCI PIPSSWAFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMM WYWGPSLYSIVSPFIPLLPIFFCLWVYI (SEQ ID NO: 4) In some embodiments, the wild-type envelope antigen is a wild-type HBV large envelope antigen encoded by the amino acid sequence of: MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIK DHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNR QSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSG TVNPAPNIASHISSISARTGDPVTNMENITSGFLGPLLVLQAGFFLLTRILTI PQSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLR 41 Attorney Docket No.45817-0192WO1 / MTX1067.20 RFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNS MFPSCCCTKPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLSLLVPFVQW FVGLSPTVWLSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLWVYI (SEQ ID NO: 5) In some embodiments, the PreS1 domain of a wild-type envelope antigen is a PreS1 domain of wild-type HBV envelope antigen encoded by the amino acid sequence of: GGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKD HWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQ SGRQPTPISPPLRDSHPQA (SEQ ID NO: 6) In some embodiments, the PreS2 domain of a wild-type envelope antigen is a PreS2 domain of wild-type HBV envelope antigen encoded by the amino acid sequence of: MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTG DPVTN (SEQ ID NO: 49) In some embodiments, the PreS1/S2 domain of a wild-type envelope antigen is a PreS1/S2 domain of wild-type HBV envelope antigen encoded by the amino acid sequence of: GGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKD HWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQ SGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGT VNPAPNIASHISSISARTGDPVTN (SEQ ID NO: 7) In some embodiments, the envelope antigen comprises one or more (i.e., at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10) mutation(s) relative to the wild-type envelope antigen encoded by SEQ ID NO: 3. In some embodiments, the envelope antigen comprises between one and 10 mutation(s) relative to the wild-type envelope antigen encoded by SEQ ID NO: 3. In some embodiments, the envelope antigen comprises 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more mutation(s) relative to the wild-type envelope antigen encoded by SEQ ID NO: 3. 42 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the HBV envelope antigen comprises a signal peptide. In some embodiments, the signal peptide is a cytomegalovirus UL130 Protein signal peptide. In some embodiments, a first open reading frame (ORF) including a nucleic acid sequence encoding the HBV envelope antigen further comprises a nucleic acid sequence encoding a signal peptide. In some embodiments, the first ORF comprises a PreS1/S2 and a signal peptide. In some embodiments, the first ORF comprises a small envelope antigen and a cytomegalovirus UL130 Protein signal peptide. In some embodiments, the first ORF comprises a PreS1/S2 and a cytomegalovirus UL130 Protein signal peptide. In some embodiments, the first open reading frame (ORF) including a nucleic acid sequence encoding the HBV envelope antigen further comprises a nucleic acid sequence encoding a linker. In some embodiments, the first ORF comprises a small envelope antigen and a linker. In some embodiments, the first ORF comprises a PreS2 and a linker. In some embodiments, the first ORF comprises a PreS1/S2 and a linker. In some embodiments, the HBV Envelope antigen is soluble. In some embodiments, the HBV Envelope antigen comprises a small Envelope antigen and is soluble. In some embodiments, the HBV Envelope antigen comprises a PreS1/S2 and is soluble. In some embodiments, the first ORF comprises and HBV Envelope antigen and a lumazine synthase domain. In some embodiments, the first ORF comprises a small Envelope antigen and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreS1/S2 and a lumazine synthase domain. In some embodiments, the lumazine synthase domain comprises the amino acid sequence of: MQIYEGKLTAEGLRFGIVASRANHALVDRLVEGAIDAIVRHGGREEDITL VRVCGSWEIPVAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKGLA DLSLELRKPITFGVITADTLEQAIEAAGTCHGNKGWEAALCAIEMANLFKS LR (SEQ ID NO: 13) 43 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the first ORF comprises a PreS1/S2, a signal peptide, a linker, and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreS1/S2, a cytomegalovirus UL130 Protein signal peptide, a linker, and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreS1/S2, the cytomegalovirus UL130 Protein signal peptide (SEQ ID NO: 9), a linker, and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreS1/S2, the cytomegalovirus UL130 Protein signal peptide (SEQ ID NO: 9), a linker, and the lumazine synthase domain of SEQ ID NO: 13. In some embodiments, the first ORF comprises a PreS1/S2, a signal peptide, a linker sequence of GSGSA (SEQ ID NO: 15), and a lumazine synthase domain of SEQ ID NO: 13. In some embodiments, the first ORF comprises a PreS1/S2, a cytomegalovirus UL130 Protein signal peptide, a linker sequence of GSGSA (SEQ ID NO: 15), and a lumazine synthase domain of SEQ ID NO: 13. In some embodiments, the first ORF comprises a PreS1/S2, the cytomegalovirus UL130 Protein signal peptide (SEQ ID NO: 9), a linker sequence of GSGSA (SEQ ID NO: 15), and a lumazine synthase domain of SEQ ID NO: 13. Table 1A. Vaccine Sequences and Naturally Occurring Protein Sequences Name Sequence SEQ ID NO: Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: ACCAACAUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGU Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GCCCGACCUCUUGCCCACCCAUCUGCCCCGGCUACCGGUGGAUGUGC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: UACUGCUCUUGUGCCUGAUCUUCUUACUUGUGCUGCUGGACUACCA Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: UACCAGGGCAUGCUGCCCGUGUGUCCUCUGAUCCCCGGCAGCACCAC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: AAGGGCAAGGACCACGCCACCUUCAACUUCCUGCAGUGGUACGUGA Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: AGGSSSGTVNPAPNIASHISSISARTGDPVTNGGSGGMLSKDIIKLLNEQVNKEMNS 50 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: mRNA ORF AUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGUGCUGCA 36 51 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLS Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: CGGCUUCCUGGGCCCUCUGCUGGUGCUGGCCGCCGGCUUCUUCCUGC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: CCAGCAUCAGCGCCCCUGAGCACAAGUUCGAGGGCCUGACCCAGAUC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: UL130sigP Pre S1 HATM Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GGGCGCCAUCGACGCCAUAGUCCGGCACGGCGGCAGAGAGGAGGAC 56 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: UCGAGGCCGCCGGCACUUGCCACGGCAACAAGGGCUGGGAGGCCGCC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GUGAGCAUCCCCUGGACCCACAAGGUGGGCAACUUCACCGGCCUGGC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: 3' UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGG 58 59 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC 65 60 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: Chemical ^{1-methylpseudouridine} Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GACCGGCGACCCAGUGCCCAACGGCAGCGGAAGCGCCAUGCAGAUCUACGAG Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: LTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSSTFHQALLDPRVRGLYF 63 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACCGUGGAGCUGCU 43 64 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: SEQ ID NO: 369 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 54 mRNA ORF SEQ ID NO: 369 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: Cap 7mG(5’)ppp(5’)NlmpNp Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: CGAGCUGAUGACCCUGGCCACCUGGGUGGGCAACAACCUGGAGGACC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC 65 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: Core149-Y132A Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: ACCAGAGCCCUCUGCGGAAGGCCGCCUACCCCGCAGUGAGCACCUUC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: KIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHL Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: AGAGCGUGCAGCACCUGGAGAGCCUGUUCACCGCCGUGACCAACUUC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: ACCUGAACCGGCGGGUGGCCGAAGACCUGAACCUGGGCAACCUGAAC 73 Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: CCCGAUCGGGUGCACUUCGCCAGCCCACUUCACGUUGCCUGGCGGCC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: CGAGCGCCGGAAGCCAGAGCCAGGGCAGCGUGUUCAGCGCCUGGUG Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GTLPQDHIVQKIKHCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPAL Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: UUGAACUUCAUGGGCUACGUGAUCGGCAGUUGGGGAACCCUGCCCC Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: GCGGCGGCUGAAGCUGAUCAUGCCCGCCCGGUUCUAUCCCAAUCUGACCAAG Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: ILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLES Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: AAGCGGAGCCAACAUCCUGGGCACCGACAAUAGCGUGGUGCUGAGCCGAAAG Attorney Docket No.45817-0192WO1 / MTX1067.20 Name Sequence SEQ ID NO: AGCCAGUUCAGCCGGGGCAACUACCGGGUGAGCUGGCCCAAAUUCGCCGUGC Table 1B. Full Construct Sequences mRNA SEQ mRNA Sequence 8 Attorney Docket No.45817-0192WO1 / MTX1067.20 PreS1S2- 412 5′7MeGpppG2′OMeAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU LuS (A)_ 3 CUCGCAACUAGCAAGCUUUUUGUUCUCGCCAUGCUGCGGCUGUUACUGCGGCACCACU UCCAUUGCCUGCUGCUGUGCGCCGUGUGGGCCACCCCUUGCCUGGCAGGCGGUUGGAG C A U G G G C U G C G C G A C U G C A A U G A C CU C U U A C C A C U C C G C C C A G A A G C G U U A A G U G Attorney Docket No.45817-0192WO1 / MTX1067.20 UGGUGGACUUCAGCCAGUUCAGCCGGGGCAACUACCGGGUGAGCUGGCCCAAAUUCGC CGUGCCCAACCUGCAGAGCCUCACUAACUUACUGUCCUCAAAUCUUUCCUGGCUGAGC CUGGACGUGAGCGCCGCCUUCUAUCAUUUGCCGCUGCACCCAGCCGCCAUGCCACACCU G C G U U U U U A G U A C A G U G G U C U U A A Table 2. Naturally Occurring HBV Protein Sequence HBV protein Genotype Naturally Occurring Protein Sequence SEQ ID Attorney Docket No.45817-0192WO1 / MTX1067.20 RFSWLSLLVPFVQWFVGLSPTVWLSAIWMM WYWGPSLYSIVSPFIPLLPIFFCLWVYI HBV envelope _{A2 strain} ^{MENITSGFLGPLLVLQAGFFLLTRILTIPQSLD} 3 In some embodiments a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein (alone or in multimeric 84 Attorney Docket No.45817-0192WO1 / MTX1067.20 form as disclosed herein), wherein the polymerase protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%- 90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1, 29, 368, 371 or 374. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, e.g., Pol_8mut. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a core protein, wherein the core protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 2, 26, 28, and 374. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a core protein, wherein the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, e.g., Core_149. In some embodiments, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid 85 Attorney Docket No.45817-0192WO1 / MTX1067.20 sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises the amino acid sequence of SEQ ID NO: 28. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding an envelope antigen, wherein the envelope antigen comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 3-5 and 16-25. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding an envelope protein, wherein the envelope protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 24, e.g., UL130sigP_PreS1S2_LuS. In some embodiments, the envelope protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a envelope antigen, wherein the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 3, e.g., Small protein. In some embodiments, the envelope 86 Attorney Docket No.45817-0192WO1 / MTX1067.20 antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid 87 Attorney Docket No.45817-0192WO1 / MTX1067.20 sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the core protein comprises the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having 88 Attorney Docket No.45817-0192WO1 / MTX1067.20 at least 95% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the core protein comprises the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a fusion protein comprising a core protein and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ 89 Attorney Docket No.45817-0192WO1 / MTX1067.20 ID NO: 27. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises the amino acid sequence of SEQ ID NO: 27. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence 90 Attorney Docket No.45817-0192WO1 / MTX1067.20 having at least 99% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the core protein comprises the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises the amino acid sequence of SEQ ID NOS: 3 and 24. The mRNA of the present disclosure encodes an HBV protein of interest, intended to raise an immune response to HBV infection. Thus, the HBV proteins of the present disclosure are antigenic, i.e., they are antigens. Antigenicity is the ability to be specifically recognized by antibodies generated as a result of an immune response to a given substance, such as an HBV protein of the present disclosure. Thus, an antigen is a protein capable of inducing an immune response (e.g., causing an immune system to produce antibodies against the antigen). In some embodiments, an antigen is an immunogen. Immunogenicity refers to the ability of a substance to induce cellular and humoral immune responses. The compositions of the present disclosure do not comprise antigens per se, but rather comprise mRNA that have an open reading frame encoding a protein antigen (referred to herein simply as a “HBV protein”) that once delivered to subject is expressed by cells in the subject. Delivery of the mRNA is achieved by formulating the mRNA in appropriate carriers or delivery vehicles (e.g., lipid nanoparticles) such that upon administration to cells, tissues or subjects, the mRNA is taken up by cells which, in turn, express the protein(s) encoded by the mRNA. It should be understood that the term “protein” encompasses peptides (and polypeptides shorter than a full-length protein), and the term “antigen” encompasses antigenic fragments. The vaccines of the present disclosure provide a unique advantage over traditional protein-based vaccination approaches in which protein antigens are purified or produced in vitro, e.g., recombinant protein production technologies. The vaccines of the present disclosure comprise mRNA encoding the desired HBV antigen(s), which when introduced into the body, i.e., administered to a mammalian subject (for example a human) in vivo, cause the cells of the body to express the desired antigen(s). In order to facilitate delivery of the mRNA to the cells of the body, the RNA is formulated (e.g., 91 Attorney Docket No.45817-0192WO1 / MTX1067.20 encapsulated) in a lipid nanoparticle. Upon delivery and uptake by cells of the body, the RNA is translated in the cytosol and the antigens are generated by the host cell machinery. The antigens are presented by the host cells and elicit an adaptive humoral and cellular immune response. Neutralizing antibodies are directed against the expressed antigens, and hence the antigens are considered relevant target antigens for vaccine development. Many proteins have a quaternary or three-dimensional structure, which includes more than one polypeptide or several polypeptide chains that associate into an oligomeric molecule. As used herein the term “subunit” refers to a single protein molecule, for example, a polypeptide or polypeptide chain resulting from processing of a nascent protein molecule, which subunit assembles (or “coassembles”) with other protein molecules (e.g., subunits or chains) to form a protein complex. Proteins can have a relatively small number of subunits and therefore be described as “oligomeric” or can consist of a large number of subunits and therefore be described as “multimeric”. The subunits of an oligomeric or multimeric protein may be identical, homologous or totally dissimilar and dedicated to disparate tasks. Proteins or protein subunits can further comprise domains. As used herein, the term “domain” refers to a distinct functional and/or structural unit within a protein. Typically, a “domain” is responsible for a particular function or interaction, contributing to the overall role of a protein. Domains can exist in a variety of biological contexts. Similar domains (i.e., domains sharing structural, functional and/or sequence homology) can exist within a single protein or can exist within distinct proteins having similar or different functions. A protein domain is often a conserved part of a given protein tertiary structure or sequence that can function and exist independently of the rest of the protein or subunit thereof. An extracellular protein domain is a part of a protein molecule that is located outside of a cell. It is typically exposed to the extracellular environment and can interact with other proteins, molecules, or the cell envelope. A transmembrane domain is a structural component of a protein that spans the lipid bilayer of a cell membrane. 92 Attorney Docket No.45817-0192WO1 / MTX1067.20 Transmembrane domains typically include one or more alpha helices or beta strands that cross the hydrophobic lipid bilayer of the cell membrane. As used herein, the term “antigen” is distinct from the term “epitope,” which is a substructure of an antigen. An epitope of a part of an antigen to which an antibody attaches. An epitope may be a peptide, for example, a 7-10 amino acid peptide, or a carbohydrate structure. The art describes protein antigens that are delivered to subjects or immune cells in isolated form, e.g., isolated proteins, however, the design, testing, validation, and production of protein antigens can be costly and time-consuming, especially when producing proteins at large scale. By contrast, mRNA technology is amenable to rapid design and testing of mRNA encoding a variety of antigens. Moreover, rapid production of mRNA coupled with formulation in appropriate delivery vehicles (e.g., lipid nanoparticles), can proceed quickly and can rapidly produce mRNA vaccines at large scale. Potential benefit also arises from the fact that antigens encoded by the mRNAs of the present disclosure are expressed by the cells of the subject, e.g., are expressed by the human body, and thus the subject, e.g., the human body, serves as the “factory” to produce the antigens which, in turn, elicits the desired immune response. The vaccines, as provided herein, may include an mRNA or multiple RNAs encoding two or more antigens of the same or different HBV strains. Thus, the vaccines of the present disclosure may be combination vaccines that target one or more antigens of the same strain/species, or one or more antigens of different strains/species, e.g., antigens that induce immunity to organisms that are found in the same geographic areas where the risk of HBV infection is high or organisms to which an individual is likely to be exposed to when exposed to HBV. Transmembrane Domains In some embodiments, the HBV proteins encoded by the mRNA vaccines comprises a heterologous transmembrane domain. A transmembrane domain is a region of a protein that spans the lipid bilayer of a biological membrane, such as a cell membrane. Transmembrane domains are composed of hydrophobic amino acids that are 93 Attorney Docket No.45817-0192WO1 / MTX1067.20 able to interact with the hydrophobic core of the membrane, anchoring the protein to the membrane and allowing it to interact with other proteins or molecules on either side of the membrane. A transmembrane domain is “heterologous” to a protein if the protein does not naturally occur with the transmembrane domain. For example, a viral transmembrane domain is heterologous to a bacterial protein or a protein comprising a bacterial domain, such as a bacterial extracellular domain. In some embodiments, the viral transmembrane domain is from an influenza virus protein, for example, an influenza virus neuraminidase transmembrane domain. Other viral transmembrane domains may also be used to anchor HBV proteins to a host cell membrane, including without limitation, the transmembrane domain from any of the following: human immunodeficiency virus (HIV) envelope glycoprotein (Env), hepatitis C virus (HCV) envelope glycoproteins E1 and E2, herpes simplex virus (HSV) glycoprotein D (gD), and other influenza virus proteins, such as hemagglutinin, neuraminidase and M2 protein. The open reading frames (ORFs) (e.g., the first ORF, the second ORF, and the third ORF) including a nucleic acid sequence encoding HBV antigens (e.g., HBV envelope antigen, HBV core protein. And HBV polymerase) of the disclosure, in some embodiments, include a nucleic acid sequence encoding a heterologous amino terminal (N terminal) transmembrane domain. In some embodiments, the ORFS include a nucleic acid sequence encoding a heterologous carboxyl terminal (C terminal) transmembrane domain. When presented at the cell envelope, the bacterial antigens are more conformationally accurate, thereby capable of eliciting a more effective immune response. In some embodiments, the ORFs comprise a nucleic acid sequence encoding a transmembrane segment of influenza neuraminidase protein. In some embodiments, the transmembrane segment of influenza neuraminidase protein comprises the amino acid sequence of: MNPNQKIITIGSVSLTISTICFFMQIAILITTVTLHFKQ (SEQ ID NO: 8) In some embodiments, t the ORFs comprise a nucleic acid sequence encoding a transmembrane segment of influenza neuraminidase protein. In some embodiments, the 94 Attorney Docket No.45817-0192WO1 / MTX1067.20 transmembrane segment of influenza hemagglutinin protein comprises the amino acid sequence of: ILAIYSTVASSLVLLVSLGAISF (SEQ ID NO: 12) In some embodiments, the ORFs comprise a nucleic acid sequence encoding an HBV antigen(s) of the disclosure and a transmembrane domain. In some embodiments, the first ORF comprises an HBV small envelope antigen and a transmembrane domain. In some embodiments, the first ORF comprises an HBV envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8). In some embodiments, the first ORF comprises an HBV small envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8). In some embodiments, the first ORF comprises an HBV envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8) fused at the N terminal. In some embodiments, the first ORF comprises an HBV small envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8) fused at the N terminus. Signal Peptides In some embodiments, an mRNA has an open reading frame that encodes a signal peptide fused to the HBV protein. Signal peptides, comprising the N-terminal 15-60 amino acids of proteins, are typically needed for the translocation across the membrane on the secretory pathway and, thus, universally control the entry of most proteins both in eukaryotes and prokaryotes to the secretory pathway. In eukaryotes, the signal peptide of a nascent precursor protein (pre-protein) directs the ribosome to the rough endoplasmic reticulum (ER) membrane and initiates the transport of the growing peptide chain across it for processing. ER processing produces mature proteins, wherein the signal peptide is cleaved from precursor proteins, typically by an ER-resident signal peptidase of the host cell, or they remain uncleaved and function as a membrane anchor. A signal peptide may also facilitate the targeting of the protein to the cell membrane. 95 Attorney Docket No.45817-0192WO1 / MTX1067.20 A signal peptide may have a length of 15-60 amino acids. For example, a signal peptide may have a length of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 amino acids. In some embodiments, a signal peptide has a length of 20-60, 25-60, 30-60, 35- 60, 40-60, 45- 60, 50-60, 55-60, 15-55, 20-55, 25-55, 30-55, 35-55, 40-55, 45-55, 50-55, 15-50, 20-50, 25-50, 30-50, 35-50, 40-50, 45-50, 15-45, 20- 45, 25-45, 30-45, 35-45, 40-45, 15-40, 20-40, 25-40, 30-40, 35-40, 15-35, 20-35, 25-35, 30-35, 15-30, 20-30, 25-30, 15-25, 20-25, or 15-20 amino acids. Signal peptides from heterologous genes (which regulate expression of genes other than HBV proteins in nature) are known in the art and can be tested for desired properties and then incorporated into a nucleic acid of the disclosure. In some embodiments, the open reading frames (ORFs) (e.g., the first ORF, the second ORF, the third ORF) comprising nucleic acid sequences encoding the HBV antigens of the present disclosure further comprise a nucleic acid sequence encoding a signal peptide from cytomegalovirus. In some embodiments, the HBV cytomegalovirus signal peptide from cytomegalovirus UL130 Protein. In some embodiments, cytomegalovirus UL130 Protein signal peptide comprises the amino acid sequence of: MLRLLLRHHFHCLLLCAVWATPCLA (SEQ ID NO: 9) In some embodiments, the ORFs of the present disclosure further comprise a nucleic acid sequence encoding a signal peptide. In some embodiments, the first ORF comprises a nucleic acid sequence encoding an HBV small envelope antigen and a signal peptide. In some embodiments, the first ORF comprises a nucleic acid sequence encoding an HBV envelope antigen and the cytomegalovirus UL130 Protein signal peptide (SEQ ID NO: 9). In some embodiments, the first ORF comprises a nucleic acid sequence encoding an HBV small envelope antigen and the cytomegalovirus UL130 Protein signal peptide (SEQ ID NO: 9). N-Linked Glycan Site Mutations 96 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the bacterial proteins encoded by the mRNA vaccines comprises one or more N-linked glycan site mutations. N-linked glycan site mutations refer to alterations in the amino acid sequence of a protein that affect the attachment of carbohydrate molecules, or glycans, at specific sites. N-linked glycans are attached to proteins at asparagine residues that are located in a specific amino acid sequence context (NxS/T/C, where x can be any amino acid except proline). These glycans can affect the structure, stability, and function of proteins and play important roles in many biological processes. Bacterial systems rarely glycosylate proteins; however, glycosylation does occur somewhat frequently in mammalian cells. To prevent glycosylation, the mRNA described herein, in some embodiments, encodes bacterial proteins wherein residues prone to N-linked glycosylation (e.g., asparagine) have been removed, modified, or substituted in order to prevent glycosylation. In some embodiments, the HBV antigens encoded by the mRNA of the disclosure comprise an HBV envelope antigen comprising one or more N-linked glycan site mutations. In some embodiments, the HBV small envelope antigen comprises one or more N-linked glycan site mutations. Fusion Proteins In some embodiments, an mRNA encodes a fusion protein. Thus, an encoded protein may include two or more proteins (e.g., protein and/or protein fragment) joined together with or without a linker. Fusion proteins, in some embodiments, retain the functional property of each independent (nonfusion) protein. In some embodiments, the mRNA encodes a fusion protein comprised of one or more HBV antigens. In some embodiments, the mRNA encodes a fusion protein comprised of two or more HBV antigens. In some embodiments, the fusion protein comprises an HBV envelope antigen comprising PreS1, PreS2, and a lumazine synthase domain. In some embodiments, the fusion protein comprises and HBV envelope antigen, and a lumazine synthase. In some embodiments, the fusion protein comprises an HBV envelope antigen that is PreS1PreS2. In some embodiments, the fusion protein comprises an HBV PreS1PreS2 and a lumazine 97 Attorney Docket No.45817-0192WO1 / MTX1067.20 synthase. In some embodiments, the fusion protein has prolonged presentation by antigen presenting cells (APC) to B cells in the context of germinal center reaction, which improves antigen-specific antibody response. Accordingly, the fusion proteins are highly immunogenic. In some embodiments, the fusion protein comprises an HBV envelope antigen and an HBV core protein. In some embodiments, the fusion protein comprises an HBV envelope antigen PreS1S2 and HBV core protein. In some embodiments, the HBV PreS1/S2 and core protein displays PreS1S2 as a large protein nanoparticle (90-mer or 120-mer) with benefits for B cell immune response and is monovalent. In some embodiments, the HBV envelope antigen PreS1S2 and HBV core protein is highly immunogenic. In some embodiments a single mRNA encoding fusion protein PreS1S2 and Core assembly domain (aa 1-149, also referred as Core149), was designed to exploit the self-assembly property of core protein to generate a nanoparticulate antigen without using antigens from other organisms (such as Lumazine Synthase and Ferritin). The design was useful for displaying PreS1S2 as a large protein nanoparticle (90-mer or 120- mer) for inducing an effective B cell immune response. These mRNA are highly immunogenic in mice (Example 5). mRNA was also used to encode VLP (virus like particles) by combining Large (PreS1-PreS2-Small), Medium (PreS2-Small), and Small Envelope sequences at different ratios, which allowed for the assembly of antigen into large particulate antigen structures similar to the natural virion particles produced by infected cells. These mRNAs were highly immunogenic in mice, (Examples). Protein variants and alignment Some embodiments relate to proteins having one or more mutations (e.g., substitutions) relative to a reference amino acid sequence and/or numbered according to a listed amino acid sequence. Some embodiments relate to amino acid or nucleotide sequences having a specified percentage sequence identity to a comparator amino acid or nucleotide 98 Attorney Docket No.45817-0192WO1 / MTX1067.20 sequence, respectively. The term “identity” refers to a relationship between the sequences of two or more polypeptides (e.g. antigens) or polynucleotides (nucleic acids), as determined by comparing the sequences. Identity also refers to the degree of sequence relatedness between or among sequences as determined by the number of matches between strings of two or more amino acid residues or nucleic acid residues. “Percent (%) identity” or “percent (%) sequence identity” as it applies to polypeptide or polynucleotide sequences is defined as the percentage of residues (amino acid residues or nucleic acid residues) in the candidate amino acid or nucleic acid sequence that are identical with the residues in the amino acid sequence or nucleic acid sequence of a second sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity. The percent sequence identity that a candidate sequence (e.g., as present in a claimed protein or nucleic acid) has to a comparator sequence (e.g., having a SEQ ID NO: specified herein) is calculated by (i) aligning the candidate sequence to the comparator sequence, (ii) determining the number of matching residues (amino acids or nucleotides) between the aligned candidate and comparator sequences, and (iii) dividing the number of matching residues by the length of the comparator sequence, including any gaps introduced into the comparator sequence when the two sequences are aligned. The skilled artisan will appreciate that to determine whether a candidate protein or nucleic acid comprises an amino acid sequence or nucleotide sequence with a given percentage sequence identity to a comparator sequence, the denominator (length of comparator sequence plus internal gaps) in calculating sequence identity need not include gaps shown at the ends of the comparator sequence in an alignment, as such gaps are added where a candidate sequence contains additional amino acids or nucleotides that extend beyond the portions that align to the N-terminal end and/or C-terminal end (amino acid sequences), or 5′ end or 3′ end (nucleotide sequences) of the comparator sequence. Where an alignment between two sequences is contemplated, the first sequence (e.g., candidate sequence) is aligned to the second sequence (e.g., comparator sequence) using the Needleman-Wunsch algorithm for global alignment of the two sequences. 99 Attorney Docket No.45817-0192WO1 / MTX1067.20 Needleman & Wunsch, J Mol Biol.1970.48:443–453. Where two protein sequences are aligned, the Needleman-Wunsch algorithm uses a BLOSUM62 substitution scoring matrix, a Gap Open penalty of 10, a Gap Extend penalty of 0.5, and no End Gap penalties. Where two nucleotide sequences are aligned, the alignment uses an DNAFULL substitution scoring matrix, a Gap Open penalty of 10, a Gap Extend penalty of 0.5, and no End Gap penalties. The skilled artisan will appreciate that at the time of filing the instant specification, these parameters are the default parameters of the EMBOSS Needle pairwise comparison tool provided by European Bioinformatics Institute (see ebi.ac.uk). Other suitable alignment programs may be used to obtain a global alignment using these parameters, such as BLAST, or the Needleman-Wunsch algorithm may be implemented in a scripting language (e.g., Python). Linkers and Cleavable Peptides In some embodiments, an mRNA that encodes a fusion protein further encodes a linker located between at least one or each domain of the fusion protein. The linker may be, for example, a cleavable linker or protease-sensitive linker. In some embodiments, the linker is selected from the group consisting of F2A linker, P2A linker, T2A linker, E2A linker, and combinations thereof (see, e.g., WO 2017/127750). This family of self- cleaving peptide linkers, referred to as 2A peptides, has been described in the art (see, e.g., Kim, J.H. et al. PLoS ONE 2011;6:e18556). In some embodiments, the linker is an F2A linker. In some embodiments, the linker is a GS linker. GS linkers are polypeptide linkers that include glycine and serine amino acids repeats. They comprise flexible and hydrophilic residues and can be used to perform fusion of protein subunits without interfering in the folding and function of the protein domains, and without formation of secondary structures. In some embodiments, an mRNA encodes a fusion protein that comprises a GS linker that is 3 to 20 amino acids long. For example, the GS linker may have a length of (or have a length of at least) 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids. In some embodiments, a GS linker is (or is at least) 15 amino acids long (e.g., GGSGGSGGSGGSGGG (SEQ ID NO: 52)). In some 100 Attorney Docket No.45817-0192WO1 / MTX1067.20 embodiments, a GS linker is (or is at least) 8 amino acids long (e.g., GGGSGGGS (SEQ ID NO: 10)). In some embodiments, a GS linker is (or is at least) 7 amino acids long (e.g., GGGSGGG (SEQ ID NO: 11)). In some embodiments, a GS linker is (or is at least) 4 amino acid long (e.g., GGGS (SEQ ID NO: 14)). In some embodiments, the GS linker comprises (GGGS)n (SEQ ID NO: 365), where n is any integer from 1-5. In some embodiments, a GS linker is (or is at least) 4 amino acid long (e.g., GSGG (SEQ ID NO: 50)). In some embodiments, the GS linker comprises (GSGG)n (SEQ ID NO: 51), where n is any integer from 1-5. In some embodiments, a linker is a glycine linker, for example having a length of (or a length of at least) 3 amino acids (e.g., GGG). In some embodiments, a protein encoded by an mRNA includes two or more linkers, which may be the same or different from each other. The skilled artisan will appreciate that other art-recognized linkers may be suitable for use in the constructs of the disclosure (e.g., encoded by the nucleic acids of the disclosure). The skilled artisan will likewise appreciate that other polycistronic constructs (mRNA encoding more than one protein separately within the same molecule) may be suitable for use as provided herein. Stabilization Domains Protein stabilization domains are protein sequences or structures that can enhance the stability of a protein to various environmental stresses, such as temperature, pH, and proteolysis. Non-limiting examples of protein stabilization domains for use to stabilize an HBV protein expressed by an mRNA include: lumazine synthase, ferritin, and thioredoxin. In some embodiments, an HBV protein is fused to a lumazine synthase. Lumazine synthase is protein from bacteria and plants that can stabilize fusion partners by forming homodimers or oligomers, which can enhance the solubility and stability of the target protein. In some embodiments, an HBV protein is fused to ferritin. Ferritin is a protein found in animals, plants, and bacteria that can form a cage-like structure that can store and sequester iron ions, protecting the cell from oxidative damage. Fusion of a target protein with ferritin can improve its stability and solubility. In some embodiments, an HBV protein, e.g., an E protein is fused to thioredoxin. Thioredoxin is small protein 101 Attorney Docket No.45817-0192WO1 / MTX1067.20 found in bacteria and eukaryotes that can act as a reducing agent and stabilize proteins by forming disulfide bonds. Nucleic Acids Encoding HBV Proteins Nucleic acids comprise a polymer of nucleotides (nucleotide monomers). Thus, nucleic acids are also referred to as polynucleotides. Nucleic acids may be or may include, for example, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), threose nucleic acid (TNA), glycol nucleic acid (GNA), peptide nucleic acid (PNA), locked nucleic acid (LNA, including LNA having a β-D-ribo configuration, α-LNA having an α- L-ribo configuration (a diastereomer of LNA), 2′-amino-LNA having a 2′-amino functionalization, and 2′-amino- α-LNA having a 2′-amino functionalization), ethylene nucleic acid (ENA), cyclohexenyl nucleic acid (CeNA) and/or chimeras and/or combinations thereof. mRNA of the present disclosure comprises an open reading frame (ORF) encoding an HBV protein. In some embodiments, the mRNA further comprises a 5^ untranslated region (UTR), 3^ UTR, a poly(A) tail and/or a 5^ cap analog. Messenger RNA Messenger RNA (mRNA) is RNA that encodes a (at least one) protein (a naturally-occurring, non-naturally-occurring, or modified polymer of amino acids) and can be translated to produce the encoded protein in vitro, in vivo, in situ, or ex vivo. As used herein, the term mRNA refers to conventional mRNA that does not include nucleic acid sequences encoding viral replicase proteins. The skilled artisan will appreciate that, except where otherwise noted, nucleic acid sequences set forth in the instant application may recite “T”s in a representative DNA sequence but where the sequence represents mRNA, the “T”s would be substituted for “U”s. Thus, any of the DNAs disclosed and identified by a particular sequence identification number herein also disclose the corresponding mRNA sequence complementary to the DNA, where each “T” of the DNA sequence is substituted with “U.” 102 Attorney Docket No.45817-0192WO1 / MTX1067.20 Naturally-occurring eukaryotic mRNA molecules can contain stabilizing elements, including, but not limited to, UTRs at their 5′-end (5′ UTR) and/or at their 3′- end (3′ UTR), in addition to other structural features, such as a 5′-cap structure or a 3′- poly(A) tail. Both the 5′ UTR and the 3′ UTR are typically transcribed from the genomic DNA and are elements of the premature mRNA. Characteristic structural features of mature mRNA, such as the 5′-cap and the 3′-poly(A) tail are usually added to the transcribed (premature) mRNA during mRNA processing. Untranslated Regions (UTRs) The mRNAs of the present disclosure may comprise one or more regions or parts which act or function as an untranslated region. A “5′ untranslated region” (UTR) refers to a region of an mRNA that is directly upstream (i.e., 5′) from the start codon (i.e., the first codon of an mRNA transcript translated by a ribosome) that does not encode a polypeptide. A “3′ untranslated region” (UTR) refers to a region of an mRNA that is directly downstream (i.e., 3′) from the stop codon (i.e., the codon of an mRNA transcript that signals a termination of translation) that does not encode a polypeptide. When RNA transcripts are being generated, the 5’ UTR may comprise a promoter sequence. Such promoter sequences are known in the art. It should be understood that such promoter sequences will not be present in a vaccine of the disclosure. Where mRNAs are designed to encode a (at least one) viral protein, the mRNA may comprise a 5’ UTR and/or 3’ UTR. UTRs of an mRNA are transcribed but not translated. In mRNA, the 5′ UTR starts at the transcription start site and continues to the start codon but does not include the start codon; the 3′ UTR starts immediately following the stop codon and continues until the transcriptional termination signal. There is a growing body of evidence about the regulatory roles played by the UTRs in terms of stability of the nucleic acid molecule and translation. The regulatory features of a UTR can be incorporated into the polynucleotides of the present disclosure to, among other things, enhance the stability of the molecule. The specific features can also be incorporated to ensure controlled down-regulation of the transcript in case they are 103 Attorney Docket No.45817-0192WO1 / MTX1067.20 misdirected to undesired organs sites. A variety of 5’ UTR and 3’ UTR sequences are known. It should also be understood that the mRNA of the present disclosure may include any 5’ UTR and/or any 3’ UTR. Exemplary UTR sequences include SEQ ID NOs: 53-65; however, other UTR sequences may be used or exchanged for any of the UTR sequences described herein. In some embodiments, a 5' UTR of the present disclosure comprises a sequence selected from: GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACC (SEQ ID NO: 53), GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCCGGCGC CGCCACC (SEQ ID NO: 54), GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUC GCAACUAGCAAGCUUUUUGUUCUCGCC (SEQ ID NO: 55), and GGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC (SEQ ID NO: 56). In some embodiments, a 5' UTR of the present disclosure comprises AGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCG CAACUAGCAAGCUUUUUGUUCUCGCC (SEQ ID NO:94). In some embodiments, a 3' UTR of the present disclosure comprises a sequence selected from UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA AAGUCUGAGUGGGCGGC (SEQ ID NO: 57), UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA AAGUCUGAGUGGGCGGC (SEQ ID NO: 58), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAGAUUGAGUGUAGUGACUAGUGG UCUUUGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 59), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAUUGAGACUACGGGUGGUCUUUG AAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 60), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGCAUAGACACUACGUGGUCUUUGAA 104 Attorney Docket No.45817-0192WO1 / MTX1067.20 UAAAGUCUGAGUGGGCGGC (SEQ ID NO: 61), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAGAUUGAGUGUAGUGGUGGUCUU UGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 62), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAGAUUGAGUGUAGUGACGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 63), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGUGGUCUUUGAAUAAAGUCUGAGUG GGCGGC (SEQ ID NO: 64), and UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA AAGUCUGAGUGGGCGGC (SEQ ID NO: 65). In some embodiments, a 3′ UTR comprises, in 5′-to-3′ order: (a) the nucleic acid sequence UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAG (SEQ ID NO: 66), (b) an identification and ratio determination (IDR) sequence, and (c) the nucleic acid sequence UGGUCUUUGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 67). IDR sequences are described herein in the section entitled “Identification and Ratio Determination (IDR) Sequences.” UTRs may also be omitted from the mRNA provided herein. A 5^ UTR does not encode a protein (is non-coding). Natural 5′ UTRs have features that play roles in translation initiation. They harbor signatures like Kozak sequences which are commonly known to be involved in the process by which the ribosome initiates translation of many genes. Kozak sequences have the consensus CCR(A/G)CCAUGG, where R is a purine (adenine or guanine) three bases upstream of the start codon (AUG), which is followed by another 'G'.5′UTR also have been known to form secondary structures which are involved in elongation factor binding. In some embodiments of the disclosure, a 5’ UTR is a heterologous UTR, i.e., is a UTR found in nature associated with a different ORF. In other embodiments, a 5’ UTR is a synthetic UTR, i.e., does not occur in nature. Synthetic UTRs include UTRs that have been mutated to improve their properties, e.g., which increase gene expression as well as 105 Attorney Docket No.45817-0192WO1 / MTX1067.20 those which are completely synthetic. Exemplary 5’ UTRs include Xenopus or human derived a-globin or b-globin (8278063; 9012219), human cytochrome b-245 a polypeptide, and hydroxysteroid (17b) dehydrogenase, and Tobacco etch virus (US8278063, US9012219). CMV immediate-early 1 (IE1) gene (US2014/0206753, WO2013/185069), the sequence GGGAUCCUACC (SEQ ID NO: 68) (WO2014/144196) may also be used. In other embodiments, a 5' UTR is a 5' UTR of a TOP gene lacking the 5' TOP motif (the oligopyrimidine tract) (e.g., WO2015/101414, WO2015/101415, WO2015/062738, WO2015/024667, WO2015/024667); 5' UTR element derived from ribosomal protein Large 32 (L32) gene (WO/2015101414, WO2015101415, WO/2015/062738), 5' UTR element derived from the 5' UTR of an hydroxysteroid (17-β) dehydrogenase 4 gene (HSD17B4) (WO2015024667), or a 5' UTR element derived from the 5' UTR of ATP5A1 (WO2015/024667) can be used. In some embodiments, an internal ribosome entry site (IRES) is used instead of a 5' UTR. A 3^ UTR does not encode a protein (is non-coding). Natural or wild type 3′ UTRs are known to have stretches of adenosines and uridines embedded in them. These AU rich signatures are particularly prevalent in genes with high rates of turnover. Based on their sequence features and functional properties, the AU rich elements (AREs) can be separated into three classes (Chen et al, 1995): Class I AREs contain several dispersed copies of an AUUUA motif within U-rich regions. C-Myc and MyoD contain class I AREs. Class II AREs possess two or more overlapping UUAUUUA(U/A)(U/A) nonamers. Molecules containing this type of AREs include GM-CSF and TNF-a. Class III ARES are less well defined. These U rich regions do not contain an AUUUA motif. c- Jun and Myogenin are two well-studied examples of this class. Most proteins binding to the AREs are known to destabilize the messenger, whereas members of the ELAV family, most notably HuR, have been documented to increase the stability of mRNA. HuR binds to AREs of all the three classes. Engineering the HuR specific binding sites into the 3′ UTR of nucleic acid molecules will lead to HuR binding and thus, stabilization of the message in vivo. 106 Attorney Docket No.45817-0192WO1 / MTX1067.20 Introduction, removal or modification of 3′ UTR AU rich elements (AREs) can be used to modulate the stability of mRNA of the disclosure. When engineering specific nucleic acids, one or more copies of an ARE can be introduced to make nucleic acids of the disclosure less stable and thereby curtail translation and decrease production of the resultant protein. Likewise, AREs can be identified and removed or mutated to increase the intracellular stability and thus increase translation and production of the resultant protein. Transfection experiments can be conducted in relevant cell lines, using nucleic acids of the disclosure and protein production can be assayed at various time points post- transfection. For example, cells can be transfected with different ARE-engineering molecules and by using an ELISA kit to the relevant protein and assaying protein produced at 6 hours, 12 hours, 1 day, 2 days, and 7 days post-transfection. Those of ordinary skill in the art will understand that 5’ UTRs that are heterologous or synthetic may be used with any desired 3’ UTR sequence. For example, a heterologous or synthetic 5’ UTR may be used with a synthetic 3’ UTR or with a heterologous 3’ UTR. Non-UTR sequences may also be used as regions or subregions within a nucleic acid. For example, introns or portions of introns sequences may be incorporated into regions of nucleic acid of the disclosure. Incorporation of intronic sequences may increase protein production as well as nucleic acid levels. Combinations of features may be included in flanking regions and may be contained within other features. For example, the ORF may be flanked by a 5' UTR which may contain a strong Kozak translational initiation signal and/or a 3' UTR which may include an oligo(dT) sequence for templated addition of a poly-A tail.5^ UTR may comprise a first polynucleotide fragment and a second polynucleotide fragment from the same and/or different genes such as the 5^ UTRs described in US2010/0293625 and WO2015/085318A2, each of which is herein incorporated by reference. It should be understood that any UTR from any gene may be incorporated into the regions of a nucleic acid. Furthermore, multiple wild-type UTRs of any known gene may be utilized. It is also within the scope of the present disclosure to provide artificial UTRs 107 Attorney Docket No.45817-0192WO1 / MTX1067.20 which are not variants of wild type regions. These UTRs or portions thereof may be placed in the same orientation as in the transcript from which they were selected or may be altered in orientation or location. Hence a 5′ or 3′ UTR may be inverted, shortened, lengthened, made with one or more other 5′ UTRs or 3′ UTRs. As used herein, the term “altered” as it relates to a UTR sequence, means that the UTR has been changed in some way in relation to a reference sequence. For example, a 3′ UTR or 5′ UTR may be altered relative to a wild-type/native UTR by the change in orientation or location as taught above or may be altered by the inclusion of additional nucleotides, deletion of nucleotides, swapping or transposition of nucleotides. Any of these changes producing an “altered” UTR (whether 3′ or 5′) comprise a variant UTR. In some embodiments, a double, triple or quadruple UTR such as a 5′ UTR or 3′ UTR may be used. As used herein, a “double” UTR is one in which two copies of the same UTR are encoded either in series or substantially in series. For example, a double beta-globin 3′ UTR may be used as described in US2010/0129877, which is incorporated herein by reference. It is also within the scope of the present disclosure to have patterned UTRs. As used herein “patterned UTRs” are those UTRs which reflect a repeating or alternating pattern, such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than 3 times. In these patterns, each letter, A, B, or C represent a different UTR at the nucleotide level. In some embodiments, flanking regions are selected from a family of transcripts whose proteins share a common function, structure, feature, or property. For example, polypeptides of interest may belong to a family of proteins which are expressed in a particular cell, tissue or at some time during development. The UTRs from any of these genes may be swapped for any other UTR of the same or different family of proteins to create a new polynucleotide. As used herein, a “family of proteins” is used in the broadest sense to refer to a group of two or more polypeptides of interest which share at least one function, structure, feature, localization, origin, or expression pattern. 108 Attorney Docket No.45817-0192WO1 / MTX1067.20 The untranslated region may also include translation enhancer elements (TEE). As a non-limiting example, the TEE may include those described in US 2009/0226470, herein incorporated by reference, and those known in the art. Open Reading Frames An open reading frame (ORF) is a continuous stretch of DNA or RNA beginning with a start codon (e.g., methionine (ATG or AUG)) and ending with a stop codon (e.g., TAA, TAG or TGA, or UAA, UAG or UGA). An ORF typically encodes a protein. It will be understood that the sequences disclosed herein may further comprise additional elements, e.g., 5′ and/or 3′ UTRs, but that those elements, unlike the ORF, need not necessarily be present in an mRNA of the present disclosure. 5’ End Capping In some embodiments, an mRNA comprises a 5′ terminal cap.5′-capping of polynucleotides may be completed concomitantly during an in vitro transcription reaction using, for example, the following chemical RNA cap analogs to generate the 5′-guanosine cap structure according to manufacturer protocols: 3´-O-Me-m7G(5')ppp(5') G [the ARCA cap];G(5')ppp(5')A; G(5')ppp(5')G; m7G(5')ppp(5')A; m7G(5')ppp(5')G (New England BioLabs, Ipswich, MA).5′-capping of modified mRNA may be completed post- transcriptionally using, for example, a Vaccinia Virus Capping Enzyme to generate the “Cap 0” structure: m7G(5')ppp(5')G (New England BioLabs, Ipswich, MA). Cap 1 structure may be generated using both Vaccinia Virus Capping Enzyme and a 2′-O methyl-transferase to generate: m7G(5')ppp(5')G-2′-O-methyl. Cap 2 structure may be generated from the Cap 1 structure followed by the 2′-O-methylation of the 5′- antepenultimate nucleotide using a 2′-O methyl-transferase. Cap 3 structure may be generated from the Cap 2 structure followed by the 2′-O-methylation of the 5′- preantepenultimate nucleotide using a 2′-O methyl-transferase. Enzymes may be derived from a recombinant source. Other cap analogs may be used. 109 Attorney Docket No.45817-0192WO1 / MTX1067.20 Polyadenylation Tailing A “poly(A) tail” is a region of mRNA that is downstream, e.g., directly downstream (i.e., 3′), from the 3′ UTR that contains multiple, consecutive adenosine monophosphates. A poly(A) tail may contain 10 to 300 adenosine monophosphates (SEQ ID NO: 408). It can, in some instances, comprise up to about 400 adenine nucleotides. For example, a poly(A) tail may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290 or 300 adenosine monophosphates (SEQ ID NO: 409). In some embodiments, a poly(A) tail contains 50 to 250 adenosine monophosphates (SEQ ID NO: 410). In a relevant biological setting (e.g., in cells, in vivo) the poly(A) tail functions to protect mRNA from enzymatic degradation, e.g., in the cytoplasm, and aids in transcription termination, and/or export of the mRNA from the nucleus and translation. In some embodiments, the length of the 3′-poly(A) tail may be an essential element with respect to the stability of the individual mRNA. In some embodiments, a poly(A) tail has a length of about 50, about 100, about 150, about 200, about 250, about 300, about 350, or about 400 nucleotides. In some embodiments, a poly(A) tail has a length of 100 nucleotides (SEQ ID NO: 411). Additional Stabilizing Elements mRNA provided herein, in some embodiments, includes an additional stabilizing element. Stabilizing elements may include, for example, a histone stem-loop. A stem- loop binding protein (SLBP), a 32 kDa protein has been identified. It is associated with the histone stem-loop at the 3'-end of the histone messages in both the nucleus and the cytoplasm. Its expression level is regulated by the cell cycle; it peaks during the S-phase, when histone mRNA levels are also elevated. The protein has been shown to be essential for efficient 3'-end processing of histone pre-mRNA by the U7 snRNP. SLBP continues to be associated with the stem-loop after processing, and then stimulates the translation of mature histone mRNAs into histone proteins in the cytoplasm. The RNA binding domain of SLBP is conserved through metazoa and protozoa; its binding to the histone stem-loop 110 Attorney Docket No.45817-0192WO1 / MTX1067.20 depends on the structure of the loop. The minimum binding site includes at least three nucleotides 5’ and two nucleotides 3^ relative to the stem-loop. In some embodiments, an mRNA includes an open reading frame (coding region), a histone stem-loop, and optionally, a poly(A) sequence or polyadenylation signal. The poly(A) sequence or polyadenylation signal generally should enhance the expression level of the encoded protein. The encoded protein, in some embodiments, is not a histone protein, a reporter protein (e.g., Luciferase, GFP, EGFP, β-Galactosidase, EGFP), or a marker or selection protein (e.g., alpha-Globin, Galactokinase and Xanthine:guanine phosphoribosyl transferase (GPT)). In some embodiments, an mRNA includes the combination of a poly(A) sequence or polyadenylation signal and at least one histone stem-loop, even though both represent alternative mechanisms in nature, they act synergistically to increase the protein expression beyond the level observed with either of the individual elements. The synergistic effect of the combination of poly(A) and a histone stem-loop does not depend on the order of the elements or the length of the poly(A) sequence. In some embodiments, an mRNA does not include a histone downstream element (HDE). “Histone downstream element” (HDE) includes a purine-rich polynucleotide stretch of approximately 15 to 20 nucleotides 3′ of naturally-occurring stem-loops, representing the binding site for the U7 snRNA, which is involved in processing of histone pre-mRNA into mature histone mRNA. In some embodiments, the nucleic acid does not include an intron. An mRNA may or may not contain an enhancer and/or promoter sequence, which may be modified or unmodified or which may be activated or inactivated. In some embodiments, the histone stem-loop is generally derived from histone genes and includes an intramolecular base pairing of two neighbored partially or entirely reverse complementary sequences separated by a spacer, consisting of a short sequence, which forms the loop of the structure. The unpaired loop region is typically unable to base pair with either of the stem loop elements. It occurs more often in RNA, as is a key component of many RNA secondary structures but may be present in single-stranded 111 Attorney Docket No.45817-0192WO1 / MTX1067.20 DNA as well. Stability of the stem-loop structure generally depends on the length, number of mismatches or bulges, and base composition of the paired region. In some embodiments, wobble base pairing (non-Watson-Crick base pairing) may result. In some embodiments, the at least one histone stem-loop sequence comprises a length of 15 to 45 nucleotides. In some embodiments, an mRNA has one or more AU-rich sequences removed. These sequences, sometimes referred to as AURES are destabilizing sequences found in the 3 ’UTR. The AURES may be removed from the mRNA. Alternatively, the AURES may remain in the mRNA. Sequence Optimization In some embodiments, an open reading frame encoding a protein of the disclosure is codon optimized. Codon optimization methods are known in the art. An open reading frame of any one or more of the sequences provided herein may be codon optimized. Codon optimization, in some embodiments, may be used to match codon frequencies in target and host organisms to ensure proper folding; bias GC content to increase mRNA stability or reduce secondary structures; minimize tandem repeat codons or base runs that may impair gene construction or expression; customize transcriptional and translational control regions; insert or remove protein trafficking sequences; remove/add post translation modification sites in encoded protein (e.g., glycosylation sites); add, remove or shuffle protein domains; insert or delete restriction sites; modify ribosome binding sites and mRNA degradation sites; adjust translational rates to allow the various domains of the protein to fold properly; or reduce or eliminate problem secondary structures within the polynucleotide. Codon optimization tools, algorithms and services are known in the art – non-limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA) and/or proprietary methods. In some embodiments, the open reading frame sequence is optimized using optimization algorithms. In some embodiments, a codon optimized sequence shares less than 95% sequence identity to a naturally-occurring or wild-type sequence open reading frame 112 Attorney Docket No.45817-0192WO1 / MTX1067.20 (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein antigen). In some embodiments, a codon optimized sequence shares less than 90% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally- occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares less than 85% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares less than 80% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares less than 75% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally- occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares between 65% and 85% (e.g., between about 67% and about 85% or between about 67% and about 80%) sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally- occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares between 65% and 75% or about 80% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally- occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon-optimized sequence encodes an antigen that is as immunogenic as, or more immunogenic than (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200% more), than an HBV protein encoded by a non-codon-optimized sequence. When transfected into mammalian host cells, the modified mRNAs have a stability of between 12-18 hours, or greater than 18 hours, e.g., 24, 36, 48, 60, 72, or greater than 72 hours and are capable of being expressed by the mammalian host cells. In some embodiments, a codon optimized mRNA may be one in which the levels of G/C are enhanced. The G/C-content of nucleic acid molecules (e.g., mRNA) may influence the stability of the RNA. mRNA having an increased amount of guanine (G) 113 Attorney Docket No.45817-0192WO1 / MTX1067.20 and/or cytosine (C) residues may be functionally more stable than RNA containing a large amount of adenine (A) and thymine (T) or uracil (U) nucleotides. As an example, WO02/098443 discloses a pharmaceutical composition containing an mRNA stabilized by sequence modifications in the translated region. Due to the degeneracy of the genetic code, the modifications work by substituting existing codons for those that promote greater RNA stability without changing the resulting amino acid. The approach is limited to coding regions of the mRNA. Chemically Unmodified Nucleotides In some embodiments, an mRNA is not chemically modified and comprises the standard ribonucleotides consisting of adenosine, guanosine, cytosine and uridine. In some embodiments, nucleotides and nucleosides of the present disclosure comprise standard nucleoside residues such as those present in transcribed RNA (e.g., A, G, C, or U). In some embodiments, nucleotides and nucleosides of the present disclosure comprise standard deoxyribonucleosides such as those present in DNA (e.g., dA, dG, dC, or dT). Chemically Modified Nucleotides The compositions of the present disclosure comprise, in some embodiments, an RNA having an open reading frame encoding an HBV protein, wherein the nucleic acid comprises nucleotides and/or nucleosides that can be standard (unmodified) or modified as is known in the art. In some embodiments, nucleotides and nucleosides of the present disclosure comprise modified nucleotides or nucleosides. Such modified nucleotides and nucleosides can be naturally-occurring modified nucleotides and nucleosides or non- naturally-occurring modified nucleotides and nucleosides. Such modifications can include those at the sugar, backbone, or nucleobase portion of the nucleotide and/or nucleoside as are recognized in the art. In some embodiments, a naturally-occurring modified nucleotide or nucleotide of the disclosure is one as is generally known or recognized in the art. Non-limiting 114 Attorney Docket No.45817-0192WO1 / MTX1067.20 examples of such naturally-occurring modified nucleotides and nucleotides can be found, inter alia, in the widely recognized MODOMICS database. In some embodiments, a non-naturally-occurring modified nucleotide or nucleoside of the disclosure is one as is generally known or recognized in the art. Non- limiting examples of such non-naturally-occurring modified nucleotides and nucleosides can be found, inter alia, in international publication numbers WO2013052523A1; WO2014093924A1; WO2015051173A2; WO2015051169A2; WO2015089511A2; or WO2017153936A1, each of which is herein incorporated by reference in its entirety. Hence, nucleic acids of the disclosure (e.g., DNA and RNA, such as mRNA) can comprise standard nucleotides and nucleosides, naturally-occurring nucleotides and nucleosides, non-naturally-occurring nucleotides and nucleosides, or any combination thereof. Nucleic acids of the disclosure (e.g., DNA and RNA, such as mRNA), in some embodiments, comprise various (more than one) different types of standard and/or modified nucleotides and nucleosides. In some embodiments, a particular region of a nucleic acid contains one, two or more (optionally different) types of standard and/or modified nucleotides and nucleosides. In some embodiments, a modified mRNA introduced to a cell or organism, exhibits reduced degradation in the cell or organism, respectively, relative to an unmodified nucleic acid comprising standard nucleotides and nucleosides. In some embodiments, a modified mRNA introduced into a cell or organism, may exhibit reduced immunogenicity in the cell or organism, respectively (e.g., a reduced innate response) relative to an unmodified nucleic acid comprising standard nucleotides and nucleosides. Nucleic acids (e.g., RNA, such as mRNA), in some embodiments, comprise non- natural modified nucleotides that are introduced during synthesis or post-synthesis of the nucleic acids to achieve desired functions or properties. The modifications may be present on internucleotide linkages, purine or pyrimidine bases, or sugars. The modification may be introduced with chemical synthesis or with a polymerase enzyme at 115 Attorney Docket No.45817-0192WO1 / MTX1067.20 the terminal of a chain or anywhere else in the chain. Any of the regions of a nucleic acid may be chemically modified. The present disclosure provides for modified nucleosides and nucleotides of a nucleic acid (e.g., RNA, such as mRNA). A “nucleoside” refers to a compound containing a sugar molecule (e.g., a pentose or ribose) or a derivative thereof in combination with an organic base (e.g., a purine or pyrimidine) or a derivative thereof (also referred to herein as “nucleobase”). A “nucleotide” refers to a nucleoside, including a phosphate group. Modified nucleotides may by synthesized by any useful method, such as, for example, chemically, enzymatically, or recombinantly, to include one or more modified or non-natural nucleosides. Nucleic acids can comprise a region or regions of linked nucleosides. Such regions may have variable backbone linkages. The linkages can be standard phosphodiester linkages, in which case the nucleic acids would comprise regions of nucleotides. Modified nucleotide base pairing encompasses not only the standard adenosine- thymine, adenosine-uracil, or guanosine-cytosine base pairs, but also base pairs formed between nucleotides and/or modified nucleotides comprising non-standard or modified bases, wherein the arrangement of hydrogen bond donors and hydrogen bond acceptors permits hydrogen bonding between a non-standard base and a standard base or between two complementary non-standard base structures, such as, for example, in those nucleic acids having at least one chemical modification. One example of such non-standard base pairing is the base pairing between the modified nucleotide inosine and adenine, cytosine or uracil. Any combination of base/sugar or linker may be incorporated into nucleic acids of the present disclosure. In some embodiments, modified nucleobases in nucleic acids (e.g., RNA, such as mRNA) comprise 1-methyl-pseudouridine (m1ψ), 1-ethyl-pseudouridine (e1ψ), 5- methoxy-uridine (mo5U), 5-methyl-cytidine (m5C), and/or pseudouridine (ψ). In some embodiments, modified nucleobases in nucleic acids (e.g., RNA, such as mRNA) comprise 5-methoxymethyl uridine, 5-methylthio uridine, 1-methoxymethyl pseudouridine, 5-methyl cytidine, and/or 5-methoxy cytidine. In some embodiments, the 116 Attorney Docket No.45817-0192WO1 / MTX1067.20 polyribonucleotide includes a combination of at least two (e.g., 2, 3, 4 or more) of any of the aforementioned modified nucleobases, including but not limited to chemical modifications. In some embodiments, an mRNA of the disclosure comprises 1-methyl- pseudouridine (m1ψ) substitutions at one or more or all uridine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises 1-methyl- pseudouridine (m1ψ) substitutions at one or more or all uridine positions of the nucleic acid and 5-methyl cytidine substitutions at one or more or all cytidine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises pseudouridine (ψ) substitutions at one or more or all uridine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises pseudouridine (ψ) substitutions at one or more or all uridine positions of the nucleic acid and 5-methyl cytidine substitutions at one or more or all cytidine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises uridine at one or more or all uridine positions of the nucleic acid. In some embodiments, RNAs (e.g., mRNAs) are uniformly modified (e.g., fully modified, modified throughout the entire sequence) for a particular modification. For example, a nucleic acid can be uniformly modified with 1-methyl-pseudouridine, meaning that all uridine residues in the mRNA sequence are replaced with 1-methyl- pseudouridine. Similarly, a nucleic acid can be uniformly modified for any type of nucleoside residue present in the sequence by replacement with a modified residue such as those set forth above. The nucleic acids of the present disclosure may be partially or fully modified along the entire length of the molecule. For example, one or more or all or a given type of nucleotide (e.g., purine or pyrimidine, or any one or more or all of A, G, U, C) may be uniformly modified in a nucleic acid of the disclosure, or in a predetermined sequence region thereof (e.g., in the mRNA including or excluding the poly(A) tail). In some 117 Attorney Docket No.45817-0192WO1 / MTX1067.20 embodiments, all nucleotides X in a nucleic acid of the present disclosure (or in a sequence region thereof) are modified nucleotides, wherein X may be any one of nucleotides A, G, U, C, or any one of the combinations A+G, A+U, A+C, G+U, G+C, U+C, A+G+U, A+G+C, G+U+C or A+G+C. The nucleic acid may contain from about 1% to about 100% modified nucleotides (either in relation to overall nucleotide content, or in relation to one or more types of nucleotide, i.e., any one or more of A, G, U or C) or any intervening percentage (e.g., from 1% to 20%, from 1% to 25%, from 1% to 50%, from 1% to 60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to 95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to 60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to 95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20% to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20% to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from 50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%, from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to 100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90% to 95%, from 90% to 100%, and from 95% to 100%). It will be understood that any remaining percentage is accounted for by the presence of unmodified A, G, U, or C. The mRNA may contain at a minimum 1% and at maximum 100% modified nucleotides, or any intervening percentage, such as at least 5% modified nucleotides, at least 10% modified nucleotides, at least 25% modified nucleotides, at least 50% modified nucleotides, at least 80% modified nucleotides, or at least 90% modified nucleotides. For example, the nucleic acids may contain a modified pyrimidine such as a modified uracil or cytosine. In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90% or 100% of the uracil in the nucleic acid is replaced with a modified uracil (e.g., a 5-substituted uracil). The modified uracil can be replaced by a compound having a single unique structure or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4 or more unique structures). In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 118 Attorney Docket No.45817-0192WO1 / MTX1067.20 90% or 100% of the cytosine in the nucleic acid is replaced with a modified cytosine (e.g., a 5-substituted cytosine). The modified cytosine can be replaced by a compound having a single unique structure or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4 or more unique structures). Identification and Ratio Determination (IDR) Sequences An Identification and Ratio Determination (IDR) sequence is a sequence of a biological molecule (e.g., nucleic acid or protein) that, when combined with the sequence of a target biological molecule, serves to identify the target biological molecule. Typically, an IDR sequence is a heterologous sequence that is incorporated within or appended to a sequence of a target biological molecule and can be used as a reference to identify the target molecule. Thus, in some embodiments, a nucleic acid (e.g., mRNA) comprises (i) a target sequence of interest (e.g., a coding sequence encoding an antigenic peptide or protein); and (ii) a unique IDR sequence. An RNA species (e.g., RNA having a given coding sequence) may comprise an IDR sequence that differs from the IDR sequence of other RNA species (e.g., RNA(s) having different coding sequence(s)). Each IDR sequence thus identifies a particular RNA species, and so the abundance of IDR sequences may be measured to determine the abundance of each RNA species in a composition. Use of distinct IDR sequences to identify RNA species allows for analysis of multivalent RNA compositions (e.g., containing multiple RNA species) containing RNA species with similar coding sequences and/or lengths, which could otherwise be difficult to distinguish using PCR- or chromatography-based analysis of full-length RNAs. Each RNA species in a multivalent RNA composition may comprise an IDR sequence that is not a sequence isomer of an IDR sequence of another RNA species in a multivalent RNA composition (e.g., the IDR sequence does not have the same number of adenosine nucleotides, the same number of cytosine nucleotides, the same number of guanine nucleotides, and the same number of uracil nucleotides, as another IDR sequence in the composition, even if those sequences have different sequences). Having identical 119 Attorney Docket No.45817-0192WO1 / MTX1067.20 nucleotide compositions causes sequence isomers to have the same mass, presenting a challenge to distinguishing sequence isomers using mass-based identification methods (e.g., mass spectrometry). Each RNA species in a multivalent RNA composition may comprise an IDR sequence having a mass that differs from the mass of IDR sequences of each other RNA species in a multivalent RNA composition. For example, the mass of each IDR sequence may differ from the mass of other IDR sequences by at least 9 Da, at least 25 Da, at least 25 Da, or at least 50 Da. Use of IDR sequences with distinct masses allows RNA fragments comprising different IDR sequences to be distinguished using mass-based analysis methods (e.g., mass spectrometry), which do not require reverse transcription, amplification, or sequencing of RNAs. Each RNA species in an RNA composition may comprises an IDR sequence with a different length. For example, each IDR sequence may have a length independently selected from 0 to 25 nucleotides. The length of a nucleic acid influences the rate at which the nucleic acid traverses a chromatography column, and so the use of IDR sequences of different lengths on different RNA species allows RNA fragments having different IDR sequences to be distinguished using chromatography-based methods (e.g., LC-UV). IDR sequences may be chosen such that no IDR sequence comprises a start codon, ‘AUG’. Lack of a start codon in an IDR sequence prevents undesired translation of nucleotide sequences within and/or downstream from the IDR sequence. IDR sequences may be chosen such that no IDR sequence comprises a recognition site for a restriction enzyme. In one example, no IDR sequence comprises a recognition site for XbaI, ‘UCUAG’. Lack of a recognition site for a restriction enzyme (e.g., XbaI recognition site ‘UCUAG’) allows the restriction enzyme to be used in generating and modifying a DNA template for in vitro transcription, without affecting the IDR sequence or sequence of the transcribed RNA. 120 Attorney Docket No.45817-0192WO1 / MTX1067.20 Nucleic Acid Production Chemical Synthesis Solid-phase chemical synthesis. Nucleic acids the present disclosure may be manufactured in whole or in part using solid phase techniques. Solid-phase chemical synthesis of nucleic acids is an automated method wherein molecules are immobilized on a solid support and synthesized step by step in a reactant solution. Solid-phase synthesis is useful in site-specific introduction of chemical modifications in the nucleic acid sequences. The synthesis of nucleic acids of the present disclosure by the sequential addition of monomer building blocks may be carried out in a liquid phase. The synthetic methods discussed above each has its own advantages and limitations. Attempts have been conducted to combine these methods to overcome the limitations. Such combinations of methods are within the scope of the present disclosure. The use of solid-phase or liquid-phase chemical synthesis in combination with enzymatic ligation provides an efficient way to generate long chain nucleic acids that cannot be obtained by chemical synthesis alone. Ligation Assembling nucleic acids by a ligase may also be used. DNA or RNA ligases promote intermolecular ligation of the 5’ and 3’ ends of polynucleotide chains through the formation of a phosphodiester bond. Nucleic acids such as chimeric polynucleotides and/or circular nucleic acids may be prepared by ligation of one or more regions or subregions. DNA fragments can be joined by a ligase catalyzed reaction to create recombinant DNA with different functions. Two oligodeoxynucleotides, one with a 5’ phosphoryl group and another with a free 3’ hydroxyl group, serve as substrates for a DNA ligase. Purification Purification of the nucleic acids described herein may include, but is not limited to, nucleic acid clean-up, quality assurance and quality control. Clean-up may be 121 Attorney Docket No.45817-0192WO1 / MTX1067.20 performed by methods known in the arts such as, but not limited to, AGENCOURT® beads (Beckman Coulter Genomics, Danvers, MA), poly-T beads, LNATM oligo-T capture probes (EXIQON® Inc, Vedbaek, Denmark) or HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC- HPLC). The term “purified” when used in relation to a nucleic acid such as a “purified nucleic acid” refers to one that is separated from at least one contaminant. A “contaminant” is any substance that makes another unfit, impure or inferior. Thus, a purified nucleic acid (e.g., DNA and RNA) is present in a form or setting different from that in which it is found in nature, or a form or setting different from that which existed prior to subjecting it to a treatment or purification method. A quality assurance and/or quality control check may be conducted using methods such as, but not limited to, gel electrophoresis, UV absorbance, or analytical HPLC. In some embodiments, the nucleic acids may be sequenced by methods including, but not limited to reverse-transcriptase-PCR. Quantification In some embodiments, the nucleic acids of the present disclosure may be quantified in exosomes or when derived from one or more bodily fluid. Bodily fluids include peripheral blood, serum, plasma, ascites, urine, cerebrospinal fluid (CSF), sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, broncheoalveolar lavage fluid, semen, prostatic fluid, cowper's fluid or pre- ejaculatory fluid, sweat, fecal matter, hair, tears, cyst fluid, pleural and peritoneal fluid, pericardial fluid, lymph, chyme, chyle, bile, interstitial fluid, menses, pus, sebum, vomit, vaginal secretions, mucosal secretion, stool water, pancreatic juice, lavage fluids from sinus cavities, bronchopulmonary aspirates, blastocyl cavity fluid, and umbilical cord blood. Alternatively, exosomes may be retrieved from an organ selected from the group consisting of lung, heart, pancreas, stomach, intestine, bladder, kidney, ovary, testis, skin, colon, breast, prostate, brain, esophagus, liver, and placenta. 122 Attorney Docket No.45817-0192WO1 / MTX1067.20 Assays may be performed using construct specific probes, cytometry, qRT-PCR, real-time PCR, PCR, flow cytometry, electrophoresis, mass spectrometry, or combinations thereof while the exosomes may be isolated using immunohistochemical methods such as enzyme linked immunosorbent assay (ELISA) methods. Exosomes may also be isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration, immunoabsorbent capture, affinity purification, microfluidic separation, or combinations thereof. These methods afford the investigator the ability to monitor, in real time, the level of nucleic acids remaining or delivered. This is possible because the nucleic acids of the present disclosure, in some embodiments, differ from the endogenous forms due to the structural or chemical modifications. In some embodiments, the nucleic acid may be quantified using methods such as, but not limited to, ultraviolet visible spectroscopy (UV/Vis). A non-limiting example of a UV/Vis spectrometer is a NANODROP® spectrometer (ThermoFisher, Waltham, MA). The quantified nucleic acid may be analyzed in order to determine if the nucleic acid may be of proper size, check that no degradation of the nucleic acid has occurred. Degradation of the nucleic acid may be checked by methods such as, but not limited to, agarose gel electrophoresis, HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC), liquid chromatography-mass spectrometry (LCMS), capillary electrophoresis (CE) and capillary gel electrophoresis (CGE). In Vitro Transcription cDNA encoding the polynucleotides described herein may be transcribed using an in vitro transcription (IVT) system. In vitro transcription of mRNA is known in the art and is described in International Publication WO 2014/152027, which is incorporated by reference herein in its entirety. In some embodiments, the RNA of the present disclosure 123 Attorney Docket No.45817-0192WO1 / MTX1067.20 is prepared in accordance with any one or more of the methods described in WO 2018/053209 or WO 2019/036682, each of which is incorporated by reference herein. In some embodiments, the mRNA transcript is generated using a non-amplified, linearized DNA template in an in vitro transcription reaction to generate the RNA transcript. In some embodiments, the template DNA is isolated DNA. In some embodiments, the template DNA is cDNA. In some embodiments, the cDNA is formed by reverse transcription of an RNA, for example, but not limited to HBV mRNA. In some embodiments, cells, e.g., bacterial cells, e.g., E. coli, e.g., DH-1 cells are transfected with the plasmid DNA template. In some embodiments, the transfected cells are cultured to replicate the plasmid DNA which is then isolated and purified. In some embodiments, the DNA template includes an RNA polymerase promoter, e.g., a T7 promoter located 5 ' to and operably linked to the gene of interest. In some embodiments, an in vitro transcription template encodes a 5′ untranslated (UTR) region, contains an open reading frame, and encodes a 3′ UTR and a poly(A) tail. The particular nucleic acid sequence composition and length of an in vitro transcription template will depend on the mRNA encoded by the template. In some embodiments, a nucleic acid (e.g., template DNA and/or RNA) includes 200 to 3,000 nucleotides. For example, a nucleic acid may include 200 to 500, 200 to 1000, 200 to 1500, 200 to 3000, 500 to 1000, 500 to 1500, 500 to 2000, 500 to 3000, 1000 to 1500, 1000 to 2000, 1000 to 3000, 1500 to 3000, or 2000 to 3000 nucleotides. An in vitro transcription system typically comprises a transcription buffer (e.g., with magnesium), nucleotide triphosphates (NTPs), an RNase inhibitor and a polymerase (e.g., T7 RNA polymerase). In some embodiments, one or more of the NTPs is a chemically modified NTP (e.g., with 1-methylpseudouridine or other chemical modifications described herein and/or known in the art). In some embodiments, the NTPs comprise adenosine triphosphate (ATP), cytidine triphosphate (CTP), uridine triphosphate (UTP), and guanosine triphosphate (GTP), or an analog of each respective NTP. The ratio of NTPs may vary. In some embodiments, the ratio of GTP:ATP:CTP:UTP is 1:1:1:1. In some embodiments, the amount of the GTP or 124 Attorney Docket No.45817-0192WO1 / MTX1067.20 an analogue thereof is greater than an amount of the UTP or an analogue thereof. In some embodiments, the amount of the GTP is greater than the amount of the UTP. In some embodiments, the amount of ATP is greater than the amount of UTP, and the amount of CTP is greater than the amount of UTP. In some embodiments, the amount of the GTP or an analogue thereof is greater than an amount of the UTP or an analogue thereof. In some embodiments, an IVT system comprises an at least 2:1 ratio of GTP concentration to ATP concentration, an at least 2:1 ratio of GTP concentration to CTP concentration, and an at least 4:1 ratio of GTP concentration to UTP concentration. In some embodiments, an IVT system comprises a 2:1 ratio of GTP concentration to ATP concentration, a 2:1 ratio of GTP concentration to CTP concentration, and a 4:1 ratio of GTP concentration to UTP concentration. In some embodiments, an IVT system comprises guanosine diphosphate (GDP). In some embodiments, an IVT system comprises an at least 3:1 ratio of GTP plus GDP concentration to ATP concentration, an at least 6:1 ratio of GTP plus GDP concentration to CTP concentration, and an at least 6:1 ratio of GTP plus GDP concentration to UTP concentration. The NTPs may be manufactured in house, may be selected from a supplier, or may be synthesized as described herein. The NTPs may be selected from, but are not limited to, those described herein including natural and unnatural (modified) NTPs. Any number of RNA polymerases or variants may be used in the method of the present disclosure. The polymerase may be selected from, but is not limited to, a phage RNA polymerase, e.g., a T7 RNA polymerase, a T3 RNA polymerase, a SP6 RNA polymerase, and/or mutant polymerases such as, but not limited to, polymerases able to incorporate modified nucleic acids and/or modified nucleotides, including chemically modified nucleic acids and/or nucleotides. Some embodiments exclude the use of DNase. An IVT system, in some embodiments, comprises magnesium buffer, dithiothreitol (DTT) spermidine, pyrophosphatase, and/or RNase inhibitor. In some embodiments, an IVT system omits an RNase inhibitor. An IVT system may be incubated at 25 degrees Celsius or at 37 degrees Celsius. Other temperatures may be used, depending in part on the polymerase (e.g., use of a variant polymerase). 125 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the RNA transcript is capped via enzymatic capping. In some embodiments, the RNA comprises 5' terminal cap, for example, 7mG(5’)ppp(5’)NlmpNp. Alternative mRNA Sequences In some embodiments, the compositions of the present disclosure include mRNA that encodes an HBV protein variant. Protein variants are proteins (including full length proteins and peptides) that differ in their amino acid sequence relative to a naturally occurring or reference amino acid sequence. A protein variant may possess one or more substitutions, deletions, and/or insertions at certain positions within its amino acid sequence, as compared to a naturally occurring or reference amino acid sequence. Ordinarily, protein variants have at least 50% identity to a naturally occurring or reference sequence. In some embodiments, a protein variant has at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%- 90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, identity to a naturally occurring or reference sequence. Global sequence alignment and local sequence alignment are two common methods used to compare and analyze sequences of DNA, RNA, or protein. Global sequence alignment compares the entire length of two sequences and finds the best possible alignment of the entire length of the sequences. It is useful, for example, when the two sequences being compared are similar in length and share significant homology. Local sequence alignment, on the other hand, identifies regions of similarity between sequences, allowing for gaps and mismatches in the alignment. This method is useful for identifying short regions of homology within larger sequences, and can be used to identify functional domains, protein families, and binding sites. Local alignment can be computationally more efficient than global alignment, and can be applied to sequences of different lengths. 126 Attorney Docket No.45817-0192WO1 / MTX1067.20 Unless stated otherwise herein, “percent (%) identity” between two mRNA polynucleotides or between two proteins refers to percent (%) identity determined using a global sequence alignment, comparing the length of entire sequences (e.g., entire mRNA polynucleotide, entire open reading frame of an mRNA, or entire protein encoded by an mRNA, as described herein). A protein variant encoded by an mRNA of the disclosure may contain amino acid changes that confer any of a number of desirable properties, for example, that enhance its immunogenicity, enhance its expression, and/or improve its stability or PK/PD properties in a subject. Protein variants can be made using routine mutagenesis techniques and assayed as appropriate to determine whether they possess the desired property. Assays to determine expression levels and immunogenicity of proteins, including protein variants, are well known in the art. Similarly, PK/PD properties of a protein variant can be measured using art recognized techniques, for example, by determining expression of the protein variant in a vaccinated subject over time and/or by looking at the durability of an induced immune response. The stability of a protein variant encoded by an mRNA may be measured by assaying thermal stability or stability upon urea denaturation or may be measured using in silico prediction, for example. Methods for such experiments and in silico determinations are known in the art. Other methods for determining protein variant expression levels, immunogenicity and/or PK/PD properties of a protein variant may be used. In some embodiments, an mRNA comprises an open reading frame that includes a nucleic acid sequence encoding an HBV envelope antigen comprising the amino acid sequence of any one of the sequences provided herein or comprises an amino acid sequence that has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%- 100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of the sequences provided herein. See, e.g., SEQ ID NOs: 30-42. 127 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, an mRNA comprises an open reading frame that encodes a polymerase protein comprising the amino acid sequence of any one of the sequences provided herein or comprises an amino acid sequence that has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 80%- 85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of the sequences provided herein. See, e.g., SEQ ID NOs: 47-48. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a core protein, wherein the core protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%- 95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 43, 44, and 46. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a fusion protein comprising a core protein and an envelope antigen protein, wherein the fusion protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%- 90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NO: 45, and 374. “Identity” refers to a relationship between two or among three or more sequences (e.g., amino acid sequences or nucleotide sequences) as determined by comparing the sequences to each other. Identity also refers to the degree of sequence relatedness between or among sequences as determined by the number of matches between or among strings of amino acids (polypeptides) or strings of nucleotides (polynucleotides). Identity is a measure of the percent of identical matches between the smaller of two or more 128 Attorney Docket No.45817-0192WO1 / MTX1067.20 sequences with gap alignments (if any) addressed by a particular mathematical model or computer program (e.g., “algorithms”). Identity of related polypeptides and polynucleotides can be readily calculated by known methods. “Percent (%) identity” as it applies to polypeptide or polynucleotide sequences is defined as the percentage of residues (amino acid or nucleic acid residues) in the candidate (first) polypeptide or polynucleotide sequence that are identical with the residues in a second polypeptide or polynucleotide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity. Methods and computer programs for the alignment are well known in the art. It is understood that identity depends on a calculation of percent identity but may differ in value due to gaps and penalties introduced in the calculation. Generally, variants of a particular polynucleotide or polypeptide have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to that particular naturally occurring or reference sequence as determined by sequence alignment programs and parameters described herein and known to those skilled in the art. Such tools for alignment include but are not limited to those of the BLAST suite (Altschul, S.F., et al. Nucleic Acids Res.1997;25:3389-3402); and those based on the Smith-Waterman algorithm (Smith, T.F. & Waterman, M.S. J. Mol. Biol.1981;147:195-197). A general global alignment technique based on dynamic programming is the Needleman–Wunsch algorithm (Needleman, S.B. & Wunsch, C.D. J. Mol. Biol.1920;48:443-453). A Fast Optimal Global Sequence Alignment Algorithm (FOGSAA) also has been developed that purportedly produces global alignment of nucleotide and protein sequences faster than other optimal global alignment methods, including the Needleman–Wunsch algorithm. Other non-limiting examples of global alignment tools include Needle (from EMBOSS), Clustal Omega, MUSCLE (Multiple Sequence Comparison by Log-Expectation), MAFFT (Multiple Alignment using Fast Fourier Transform), and T-Coffee (Tree-based Consistency Objective Function for Alignment Evaluation). Polynucleotides and polypeptides containing substitutions, insertions and/or deletions (e.g., indels), and covalent modifications with respect to naturally occurring or 129 Attorney Docket No.45817-0192WO1 / MTX1067.20 reference sequence, for example, the polypeptide (e.g., protein) sequences disclosed herein, are included within the scope of this disclosure. For example, sequence tags or amino acids, such as one or more lysine(s), can be added to polypeptide sequences (e.g., at the N-terminal and/or C-terminal end). Sequence tags can be used for peptide detection, purification and/or localization. Lysines can be used to increase peptide solubility or to allow for biotinylation. Alternatively, amino acid residues located at the N-terminal and/or C-terminal regions of the amino acid sequence of a protein may optionally be deleted providing for truncated sequences. Certain amino acids (e.g., C- terminal or N-terminal amino acids) may be deleted depending on the use of the sequence, as for example, expression of the sequence as part of a larger sequence that is soluble or linked to a solid support. In some embodiments, sequences for (or encoding) signal sequences, termination sequences, transmembrane domains, linkers, multimerization domains (e.g., foldon regions) and the like are substituted with alternative sequences that achieve the same or a similar function. In some embodiments, cavities in the core of proteins can be filled to improve stability, e.g., by introducing larger amino acids. In other embodiments, buried hydrogen bond networks are replaced with hydrophobic resides to improve stability. In yet other embodiments, glycosylation sites are removed and replaced with appropriate residues. Such sequences are readily identifiable to one of skill in the art. It should also be understood that some of the sequences provided herein contain sequence tags or terminal peptide sequences (e.g., at the N-terminal or C-terminal ends) that may be deleted, for example, prior to use in the preparation of an mRNA vaccine. As recognized by those skilled in the art, protein fragments, functional protein domains, and homologous proteins are also considered to be within the scope of HBV proteins provided herein. For example, provided herein is any protein fragment of (meaning a polypeptide sequence at least one amino acid residue shorter than but otherwise identical to) a naturally occurring or reference sequence, provided that the fragment is immunogenic and confers a protective immune response to LD. In addition to protein variants that are identical to the naturally occurring or reference protein but are 130 Attorney Docket No.45817-0192WO1 / MTX1067.20 truncated, in some embodiments, a protein includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations (e.g., substitutions, insertions and/or deletions), as shown in any of the sequences provided or referenced herein. Protein variants can range in length from about 4, 6, or 8 amino acids to full length proteins. Lipid Compositions In some embodiments, the nucleic acids of in (e.g., formulated as) a lipid composition, such as a composition comprising a lipid nanoparticle. In some embodiments, nucleic acids of the present disclosure are in (e.g., formulated as) lipid nanoparticle (LNP) compositions. Lipid nanoparticles typically comprise an ionizable amino lipid, non-cationic lipid (e.g., a phospholipid), structural lipid, and PEG lipid components along with the nucleic acid cargo (i.e., mRNA) of interest. A lipid nanoparticles of the present disclosure can be generated using components, compositions, and methods as are generally known in the art, see for example PCT/US2016/052352; PCT/US2016/068300; PCT/US2017/037551; PCT/US2015/027400; PCT/US2016/047406; PCT/US2016000129; PCT/US2016/014280; PCT/US2017/038426; PCT/US2014/027077; PCT/US2014/055394; PCT/US2016/52117; PCT/US2012/069610; PCT/US2017/027492; PCT/US2016/059575; PCT/US2016/069491; PCT/US2016/069493; and PCT/US2014/66242, all of which are incorporated by reference herein in their entirety. In some embodiments, a lipid nanoparticle comprises at least one ionizable amino lipid, at least one non-cationic lipid, at least one sterol, and/or at least one polyethylene glycol (PEG)-modified lipid. In some embodiments, a lipid nanoparticle comprises 20-60 mole percent (mol%) ionizable amino lipid, 5-25 mol% non-cationic lipid, 25-55 mol% structural lipid, and 0.5-15 mol% PEG-modified lipid. In some embodiments, a lipid nanoparticle comprises 20-60 mol% ionizable amino lipid, 5-30 mol% non-cationic lipid, 10-55 mol% structural lipid, and 0.5-15 mol% PEG-modified lipid. 131 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, a lipid nanoparticle comprises 40-50 mol% ionizable lipid, optionally 45-50 mol%, for example, 45-46 mol%, 46-47 mol%, 47-48 mol%, 48-49 mol%, or 49-50 mol% for example about 45 mol%, 45.5 mol%, 46 mol%, 46.5 mol%, 47 mol%, 47.5 mol%, 48 mol%, 48.5 mol%, 49 mol%, or 49.5 mol%. In some embodiments, a lipid nanoparticle comprises 20-60 mol% ionizable amino lipid. For example, a lipid nanoparticle may comprise 20-50 mol%, 20-40 mol%, 20-30 mol%, 30-60 mol%, 30-50 mol%, 30-40 mol%, 40-60 mol%, 40-50 mol%, or 50- 60 mol% ionizable amino lipid. In some embodiments, a lipid nanoparticle comprises 20 mol%, 30 mol%, 40 mol%, 50 mol%, or 60 mol% ionizable amino lipid. In some embodiments, a lipid nanoparticle comprises 35 mol%, 36 mol%, 37 mol%, 38 mol%, 39 mol%, 40 mol%, 41 mol%, 42 mol%, 43 mol%, 44 mol%, 45 mol%, 46 mol%, 47 mol%, 48 mol%, 49 mol%, 50 mol%, 51 mol%, 52 mol%, 53 mol%, 54 mol%, or 55 mol% ionizable amino lipid. In some embodiments, a lipid nanoparticle comprises 45-55 mol% ionizable amino lipid. For example, lipid nanoparticle may comprise 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55 mol% ionizable amino lipid. Ionizable amino lipids In some embodiments, the ionizable lipid is a compound of Formula (IL*) or a salt thereof, wherein: R¹ is -OH, -NR^N-C4-10 cycloalkenyl optionally substituted with one or more oxo or -N(R^N’R^N’’); 132 Attorney Docket No.45817-0192WO1 / MTX1067.20 R^N is H or C1-6 alkyl; R^N’ is H or C_1-6 alkyl; R^N’’ is H or C_1-6 alkyl; o is 1, 2, 3, or 4; n is 4, 5, 6, 7, or 8; m is 4, 5, 6, 7, or 8; M is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R²; M’ is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R³; R² is or –(C_1-6 alkylene)-(C_3-8 cycloalkyl)-C_1-6 alkyl; R^2a R^2b is -H or C1-10 alkyl; R^2c is C_1-8 alkyl or C_2-8 alkenyl; ; R^3b is H or C_1-8 alkyl; and R^3c is C1-10 alkyl or C2-8 alkenyl. In some embodiments, the ionizable lipid is of Formula (IL**-I): R^2c or a salt thereof, wherein: R¹ is -OH; o is 2, 3, or 4; 133 Attorney Docket No.45817-0192WO1 / MTX1067.20 n is 4, 5, 6, 7, or 8; M is -C(=O)-O-*, wherein * indicates attachment to R²; m is 6, 7, or 8; M’ is -C(=O)-O-*, wherein * indicates attachment to R³; R^2c is C4-8 alkyl; R^3a is C_7-10 alkyl; and R^3c is C3-5 alkyl. In some embodiments, the ionizable lipid is of Formula (IL**-III): R^2c R^2a or a salt thereof, wherein: R¹ is NR^N-C_4-10 cycloalkenyl optionally substituted with one or more oxo or - N(R^N’R^N’’); R^N is H; R^N’ is C_1-2 alkyl; R^N’’ is H; o is 2, 3, or 4; n is 6, 7, or 8; M is -C(=O)-O-*, wherein * indicates attachment to R²; m is 6, 7, or 8; M’ is -C(=O)-O-*, wherein * indicates attachment to R³; R^2a is C_7-10 alkyl; R^2c is C4-6 alkyl; R^3a is C1-3 alkyl; and 134 Attorney Docket No.45817-0192WO1 / MTX1067.20 R^3c is C4-6 alkyl. In some embodiments, the ionizable lipid is of Formula (IL**-IV): R^2b R^2c or a salt thereof, wherein: R¹ is OH; o is 2, 3, or 4; n is 6, 7, or 8; M is -C(=O)-O-*, wherein * indicates attachment to R²; m is 6, 7, or 8; M’ is -C(=O)-O-*, wherein * indicates attachment to R³; R^2b is C_3-5 alkyl; R^2c is C_2-4 alkyl; R^3a is C7-10 alkyl; and R^3c is C_4-6 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-I): R^2c or a salt thereof, wherein: 135 Attorney Docket No.45817-0192WO1 / MTX1067.20 R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for variable IL*; and R^3a is C_1-8 alkyl. In some embodiments, ionizable lipid is of Formula (IL*-Ia): or a salt thereof, wherein: R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for Formula IL*; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-Ia’): or a salt thereof, wherein: o, M, M’, R^2c and R^3c are as defined for variable IL*; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIa): or a salt thereof, R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for Formula IL*; and 136 Attorney Docket No.45817-0192WO1 / MTX1067.20 R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-II’): R2c HO _o N M or a salt thereof, o, M, M’, R^2c and R^3c are as defined for variable IL*; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-III): R^2c R^2a or a salt thereof, wherein: R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2a is a C1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIa): Attorney Docket No.45817-0192WO1 / MTX1067.20 (IL*-IIIa) or a salt thereof, wherein: R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2b is a C1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIa): or a salt thereof, wherein: R¹, o, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2a is a C1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIa’): or a salt thereof, wherein: R¹, o, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2a is a C_1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIb): 138 Attorney Docket No.45817-0192WO1 / MTX1067.20 or a salt thereof, R¹, o, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2a is a C1-8 alkyl; and R^3a is C_1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIb’): R¹, o, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2a is a C1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IV): R^2b R^2c Attorney Docket No.45817-0192WO1 / MTX1067.20 or a salt thereof, wherein: R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2b is a C_1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IVa): or a salt thereof, R¹, o, m, n, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2b is a C1-8 alkyl; and R^3a is C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-Iva’): or a salt thereof, wherein: o, M, M’, R^2c, and R^3c are as defined for variable IL*; R^2a is a C1-8 alkyl; and R^3a is C_1-8 alkyl. Variables o, R¹, R^N, R^N’, R^N’’ of Ionizable Lipid In some embodiments of the ionizable lipid, o is 1. 140 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the ionizable lipid, o is 2. In some embodiments of the ionizable lipid, o is 3. In some embodiments of the ionizable lipid, o is 4. In some embodiments of the ionizable lipid, R¹ is -OH. In some embodiments of the ionizable lipid, R^N is H. In some embodiments of the ionizable lipid, R^N is methyl. In some embodiments of the ionizable lipid, R^N is ethyl. In some embodiments of the ionizable lipid, R¹ is -NR^N-cyclobutenyl, wherein the cyclobutenyl is optionally substituted with one or more oxo or -N(R^N’R^N’’). In some embodiments of the ionizable lipid, R^N’ is H. In some embodiments of the ionizable lipid, R^N’ is methyl. In some embodiments of the ionizable lipid, R^N’ is ethyl. In some embodiments of the ionizable lipid, R^N’’ is H. In some embodiments of the ionizable lipid, R^N’’ is methyl. In some embodiments of the ionizable lipid, R^N’’ is ethyl. In some embodiments of the ionizable lipid, R^N’ is H and R^N’’ is methyl. In some embodiments of the ionizable . In some embodiments of the ionizable . Variables m and n of the Ionizable Lipid In some embodiments of the ionizable lipid, m is 4. In some embodiments of the ionizable lipid, m is 5. In some embodiments of the ionizable lipid, m is 6. In some embodiments of the ionizable lipid, m is 7. In some embodiments of the ionizable lipid, m is 8. 141 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the ionizable lipid, m is 4. In some embodiments of the ionizable lipid, n is 5. In some embodiments of the ionizable lipid, n is 6. In some embodiments of the ionizable lipid, n is 7. In some embodiments of the ionizable lipid, n is 8. In some embodiments of the ionizable lipid, n is 5 and m is 7. In some embodiments of the ionizable lipid, n is 7 and m is 7. In some embodiments of the ionizable lipid, m is 6 and n is 6. Variables M and M’ In some embodiments of the ionizable lipid, M is -O-C(=O)-*, wherein * indicates attachment to R². In some embodiments of the ionizable lipid, M is -C(=O)-O-* wherein * indicates attachment to R². In some embodiments of the ionizable lipid, M’ is -O-C(=O)-*, wherein * indicates attachment to R³. In some embodiments of the ionizable lipid, M’ is -C(=O)-O-* wherein * indicates attachment to R³. In some embodiments of the ionizable lipid, M is -O-C(=O)-*, wherein * indicates attachment to R², and M’ is -C(=O)-O-* wherein * indicates attachment to R³ Variables R², R^2a, R^2b, R^2c In some embodiments of the ionizable . In some embodiments of the ionizable In some embodiments of the ionizable lipid, R^2a is methyl. In some embodiments of the ionizable lipid, R^2a is ethyl. In some embodiments of the ionizable lipid, R^2a is propyl. In some embodiments of the ionizable lipid, R^2a is butyl. 142 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the ionizable lipid, R^2a is pentyl. In some embodiments of the ionizable lipid, R^2a is hexyl. In some embodiments of the ionizable lipid, R^2a is heptyl. In some embodiments of the ionizable lipid, R^2a is octyl. In some embodiments of the ionizable lipid, R^2b is hydrogen. In some embodiments of the ionizable lipid, R^2b is methyl. In some embodiments of the ionizable lipid, R^2b is ethyl. In some embodiments of the ionizable lipid, R^2b is propyl. In some embodiments of the ionizable lipid, R^2b is butyl. In some embodiments of the ionizable lipid, R^2b is pentyl. In some embodiments of the ionizable lipid, R^2b is hexyl. In some embodiments of the ionizable lipid, R^2b is heptyl. In some embodiments of the ionizable lipid, R^2b is octyl. In some embodiments of the ionizable lipid, R^2a is hydrogen and R^2b is hydrogen. In some embodiments of the ionizable lipid, R^2a is hexyl and R^2b is hydrogen. In some embodiments of the ionizable lipid, R^2a is octyl and R^2b is hydrogen. In some embodiments of the ionizable lipid, R^2a is hydrogen and R^2b is butyl. In some embodiments of the ionizable lipid, R^2c is methyl. In some embodiments of the ionizable lipid, R^2c is ethyl. In some embodiments of the ionizable lipid, R^2c is propyl. In some embodiments of the ionizable lipid, R^2c is butyl. In some embodiments of the ionizable lipid, R^2c is pentyl. In some embodiments of the ionizable lipid, R^2c is hexyl. In some embodiments of the ionizable lipid, R^2c is heptyl. In some embodiments of the ionizable lipid, R^2c is octyl. In some embodiments of the ionizable lipid, R² is –(C_1-6 alkylene)-(C_3-8 cycloalkyl)-C1-6 alkyl. In some embodiments of the ionizable lipid, R² is –(C1-6 alkylene)-(cyclohexyl)- C_1-6 alkyl. 143 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the ionizable lipid, R² is –(C1-6 alkylene)-(cyclopentyl)- C_1-6 alkyl. Variables R³, R^3a, R^3b, and R^3c I_{n some embodiments of the ionizable lipid, .} In some embodiments of the ionizable lipid, In some embodiments of the ionizable lipid, R^3a is methyl. In some embodiments of the ionizable lipid, R^3a is ethyl. In some embodiments of the ionizable lipid, R^3a is propyl. In some embodiments of the ionizable lipid, R^3a is butyl. In some embodiments of the ionizable lipid, R^3a is pentyl. In some embodiments of the ionizable lipid, R^3a is hexyl. In some embodiments of the ionizable lipid, R^3a is heptyl. In some embodiments of the ionizable lipid, R^3a is octyl. In some embodiments of the ionizable lipid, R^3b is hydrogen. In some embodiments of the ionizable lipid, R^3b is methyl. In some embodiments of the ionizable lipid, R^3b is ethyl. In some embodiments of the ionizable lipid, R^3b is propyl. In some embodiments of the ionizable lipid, R^3b is butyl. In some embodiments of the ionizable lipid, R^3b is pentyl. In some embodiments of the ionizable lipid, R^3b is hexyl. In some embodiments of the ionizable lipid, R^3b is heptyl. In some embodiments of the ionizable lipid, R^3b is octyl. In some embodiments of the ionizable lipid, R^3a is octyl and R^3b is hydrogen. In some embodiments of the ionizable lipid, R^3a is ethyl and R^3b is hydrogen. In some embodiments of the ionizable lipid, R^3a is hexyl and R^3b is hydrogen. In some embodiments of the ionizable lipid, R^3c is methyl. In some embodiments of the ionizable lipid, R^3c is ethyl. 144 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments of the ionizable lipid, R^3c is propyl. In some embodiments of the ionizable lipid, R^3c is butyl. In some embodiments of the ionizable lipid, R^3c is pentyl. In some embodiments of the ionizable lipid, R^3c is hexyl. In some embodiments of the ionizable lipid, R^3c is heptyl. In some embodiments of the ionizable lipid, R^3c is octyl. It is understood that, for an ionizable lipid, variables o, R¹, R^N, R^N’, R^N’, m, n, M, M’, R², R^2a, R^2b, R^2c, R³, R^3a, R^3b, and R^3c can each be, where applicable, selected from the groups described herein, and any group described herein for any of variables o,.R¹, R^N, R^N’, R^N’, m, n, M, M’, R², R^2a, R^2b, R^2c, R³, R^3a, R^3b, and R^3c can be combined, where applicable, with any group described herein for one or more of the remainder of variables o, R¹, R^N, R^N’, R^N’, m, n, M, M’, R², R^2a, R^2b, R^2c, R³, R^3a, R^3b, and R^3c. In some embodiments, the ionizable lipid is a compound selected from: , 6), . is 145 Attorney Docket No.45817-0192WO1 / MTX1067.20 . is . . it is understood that an ionizable lipid may a or at physiological pH. Such lipids may be referred to as cationic or ionizable (amino)lipids. Lipids may also be zwitterionic, i.e., neutral molecules having both a positive and a negative charge. mRNA-Lipid Adduct It has been determined that certain ionizable lipids are susceptible to the formation of lipid-polynucleotide adducts. In particular, ionizable lipids that comprise a tertiary amine group may decompose into one or both of a secondary amine and a reactive aldehyde species capable of interacting with polynucleotides (such as mRNA) to form an ionizable lipid-polynucleotide adduct impurity that can be detected by reverse phase ion pair chromatography (RP-IP HPLC). For example, oxidation of the tertiary amine may lead to N-oxide formation that can undergo acid/base-catalyzed hydrolysis at the amine to generate aldehydes and secondary amines which may form adducts with mRNA. Thus, in some aspects, the ionizable lipid-polynucleotide adduct impurity is an aldehyde-mRNA adduct impurity. It also has been determined that such adducts may disrupt mRNA translation and impact the activity of lipid nanoparticle (LNP) formulated mRNA products. Thus, it can be advantageous to prepare and use LNP compositions with a reduced content of 146 Attorney Docket No.45817-0192WO1 / MTX1067.20 ionizable lipid-polynucleotide adduct impurity, such as wherein less than about 20%, less than about 10%, less than about 5%, or less than about 1%, of the mRNA is in the form of ionizable lipid-polynucleotide adduct impurity, as may be measured by RP-IP HPLC. Thus, in accordance with some aspects, an LNP composition is provided wherein less than about 10%, less than about 5%, or less than about 1%, of the mRNA is in the form of ionizable lipid-polynucleotide adduct impurity, including less than 10%, less than 5%, or less than 1%, as may be measured by RP-IP HPLC. In some aspects, an amount of lipid aldehydes in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of N-oxide compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of transition metals, such as Fe, in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of alkyl halide compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of anhydride compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of ketone compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of conjugated diene compounds in the composition is less than about 50 ppm, including less than 50 ppm. In some aspects, the composition is stable against the formation of ionizable lipid- polynucleotide adduct impurity. In some aspects, an amount of ionizable lipid- polynucleotide adduct impurity in the composition increases at an average rate of less than about 2% per day when stored at a temperature of about 25 °C or below, including at an average rate of less than 2% per day. In some aspects, an amount of ionizable lipid- polynucleotide adduct impurity in the composition increases at an average rate of less than about 0.5% per day when stored at a temperature of about 5 °C or below, including at an average rate of less than 0.5% per day. In some aspects, an amount of ionizable lipid-polynucleotide adduct impurity in the composition increases at an average rate of 147 Attorney Docket No.45817-0192WO1 / MTX1067.20 less than about 0.5% per day when stored at a refrigerated temperature, optionally wherein the refrigerated temperature is about 5 °C. Lipid vehicle (e.g., LNP) compositions with a reduced content of ionizable lipid- polynucleotide adduct impurity can be prepared by methods that inhibit formation of one or both of N-oxides and aldehydes. Such methods may comprise treating a composition comprising an ionizable lipid comprising a tertiary amine group to inhibit formation of one or both of N-oxides and aldehydes, such as by treating the composition with a reducing agent; treating the composition with a chelating agent; adjusting the pH of the composition; adjusting the temperature of the composition; and adjusting the buffer in the composition. Such methods may comprise, prior to combining the ionizable lipid with a polynucleotide, one or more of treating the ionizable lipid with a scavenging agent; treating the ionizable lipid with a reductive treatment agent; treating the ionizable lipid with a reducing agent; treating the ionizable lipid with a chelating agent; treating the polynucleotide with a reducing agent; and treating the polynucleotide with a chelating agent. In accordance with any of the foregoing, the scavenging agent, reductive treatment agent, and/or reducing agent may be an agent that reacts with aldehyde, ketone, anhydride and/or diene compounds. A scavenging agent may comprise one or more selected from (O-(2,3,4,5,6-Pentafluorobenzyl)hydroxylamine hydrochloride) (PFBHA), methoxyamine (e.g., methoxyamine hydrochloride), benzyloxyamine (e.g., benzyloxyamine hydrochloride), ethoxyamine (e.g., ethoxyamine hydrochloride), 4-[2- (aminooxy)ethyl]morpholine dihydrochloride, butoxyamine (e.g., tert-butoxyamine hydrochloride), 4-Dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), Triethylamine (TEA), Piperidine 4-carboxylate (BPPC), and combinations thereof. A reductive treatment agent may comprise a boron compound (e.g., sodium borohydride and/or bis(pinacolato)diboron). A reductive treatment agent may comprise a boron compound, such as one or both of sodium borohydride and bis(pinacolato)diboron). A chelating agent may comprise immobilized iminodiacetic acid. A reducing agent may comprise an immobilized reducing agent, such as 148 Attorney Docket No.45817-0192WO1 / MTX1067.20 immobilized diphenylphosphine on silica (Si-DPP), immobilized thiol on agarose (Ag- Thiol), immobilized cysteine on silica (Si-Cysteine), immobilized thiol on silica (Si- Thiol), or a combination thereof. A reducing agent may comprise a free reducing agent, such as potassium metabisulfite, sodium thioglycolate, tris(2-carboxyethyl)phosphine (TCEP), sodium thiosulfate, N-acetyl cysteine, glutathione, dithiothreitol (DTT), cystamine, dithioerythritol (DTE), dichlorodiphenyltrichloroethane (DDT), homocysteine, lipoic acid, or a combination thereof. In accordance with any of the foregoing, the pH may be, or adjusted to be, a pH of from about 7 to about 9 (for example, about 7, about 7.5, about 8, about 8.5, or about 9). In accordance with any of the foregoing, a buffer may be selected from sodium phosphate, sodium citrate, sodium succinate, histidine, histidine-HCl, sodium malate, sodium carbonate, and TRIS (tris(hydroxymethyl)aminomethane). In accordance with any of the foregoing, a buffer may be TRIS and may be, or adjusted to be, from about 20 mM to about 150 mM TRIS. In accordance with any of the foregoing, the temperature of the composition may be, or adjusted to be, 25 ⁰C or less. The composition may also comprise a free reducing agent or antioxidant. Phospholipids In some embodiments, a lipid nanoparticle comprises 5-25 mol% non-cationic lipid. For example, a lipid nanoparticle may comprise 5-20 mol%, 5-15 mol%, 5-10 mol%, 10-25 mol%, 10-20 mol%, 10-25 mol%, 15-25 mol%, 15-20 mol%, or 20-25 mol% non-cationic lipid. In some embodiments, a lipid nanoparticle comprises 5 mol%, 10 mol%, 15 mol%, 20 mol%, or 25 mol% non-cationic lipid. In some embodiments, a non-cationic lipid of the disclosure comprises 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-gly cero-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3- phosphocholine (DOPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2- 149 Attorney Docket No.45817-0192WO1 / MTX1067.20 diundecanoyl-sn-glycero-phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC), 1-oleoyl-2 cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2- dilinolenoyl-sn-glycero-3-phosphocholine,1,2-diarachidonoyl-sn-glycero-3- phosphocholine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-diphytanoyl- sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2- dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3- phosphoethanolamine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2- dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), sphingomyelin, or mixtures thereof. In some embodiments, a lipid nanoparticle comprises 5 – 15 mol%, 5 – 10 mol%, or 10 – 15 mol% DSPC. For example, a lipid nanoparticle may comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 mol% DSPC. In certain embodiments, the lipid composition of a lipid nanoparticle composition disclosed herein can comprise one or more phospholipids, for example, one or more saturated or (poly)unsaturated phospholipids or a combination thereof. In general, phospholipids comprise a phospholipid moiety and one or more fatty acid moieties. A phospholipid moiety can be selected, for example, from the non-limiting group consisting of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl glycerol, phosphatidyl serine, phosphatidic acid, 2-lysophosphatidyl choline, and a sphingomyelin. A fatty acid moiety can be selected, for example, from the non-limiting group consisting of lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, erucic acid, phytanoic acid, arachidic acid, arachidonic acid, eicosapentaenoic acid, behenic acid, docosapentaenoic acid, and docosahexaenoic acid. Particular phospholipids can facilitate fusion to a membrane. For example, a cationic phospholipid can interact with one or more negatively charged phospholipids of 150 Attorney Docket No.45817-0192WO1 / MTX1067.20 a membrane (e.g., a cellular or intracellular membrane). Fusion of a phospholipid to a membrane can allow one or more elements (e.g., an mRNA) of a lipid-containing composition (e.g., LNPs) to pass through the membrane permitting, e.g., delivery of the one or more elements to a target tissue. Non-natural phospholipid species including natural species with modifications and substitutions including branching, oxidation, cyclization, and alkynes are also contemplated. For example, a phospholipid can be functionalized with or cross-linked to one or more alkynes (e.g., an alkenyl group in which one or more double bonds is replaced with a triple bond). Under appropriate reaction conditions, an alkyne group can undergo a copper-catalyzed cycloaddition upon exposure to an azide. Such reactions can be useful in functionalizing a lipid bilayer of a nanoparticle composition to facilitate membrane permeation or cellular recognition or in conjugating a nanoparticle composition to a useful component such as a targeting or imaging moiety (e.g., a dye). Phospholipids include, but are not limited to, glycerophospholipids such as phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, phosphatidylinositols, phosphatidylglycerols, and phosphatidic acids. Phospholipids also include phosphosphingolipid, such as sphingomyelin. In some embodiments, a phospholipid of the present disclosure comprises 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-Distearoyl-sn-glycero-3- phosphoethanolamine (DSPE), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-gly cero- phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), l,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-diundecanoyl-sn-glycero- phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC), 1-oleoyl-2 cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), 1-hexadecyl-sn- glycero-3-phosphocholine (C16 Lyso PC), 1,2-dilinolenoyl-sn-glycero-3- phosphocholine,1,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1,2- didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-diphytanoyl-sn-glycero-3- 151 Attorney Docket No.45817-0192WO1 / MTX1067.20 phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3- phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2- didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3- phospho-rac-(1-glycerol) sodium salt (DOPG), sphingomyelin, or mixtures thereof. In certain embodiments, a phospholipid useful or potentially useful in the present disclosure is an analog or variant of DSPC. In certain embodiments, a phospholipid useful or potentially useful in the present disclosure is a compound of Formula (IX): , substituted alkyl; or optionally two R¹ are joined together with the intervening atoms to form optionally substituted monocyclic carbocyclyl or optionally substituted monocyclic heterocyclyl; or optionally three R¹ are joined together with the intervening atoms to form optionally substituted bicyclic carbocyclyl or optionally substitute bicyclic heterocyclyl; n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; A is of the ; each instance of L² substituted C1-6 alkylene, wherein one methylene unit of the optionally substituted C1-6 alkylene is optionally replaced with O, N(R^N), S, C(O), C(O)N(R^N), NR^NC(O), C(O)O, OC(O), - OC(O)O, OC(O)N(R^N), NR^NC(O)O, or NR^NC(O)N(R^N); each instance of R² is independently optionally substituted C1-30 alkyl, optionally substituted C_1-30 alkenyl, or optionally substituted C_1-30 alkynyl; optionally wherein one or more methylene units of R² are independently replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, 152 Attorney Docket No.45817-0192WO1 / MTX1067.20 optionally substituted heteroarylene, N(R^N), O, S, C(O), C(O)N(R^N), NR^NC(O), - NR^NC(O)N(R^N), C(O)O, OC(O), OC(O)O, OC(O)N(R^N), NR^NC(O)O, C(O)S, SC(O), - , , , , 2, - N(R^N)S(O)₂, S(O)₂N(R^N), N(R^N)S(O)₂N(R^N), OS(O)₂N(R^N), or N(R^N)S(O)₂O; each instance of R^N is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group; Ring B is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and p is 1 or 2; provided that the compound is not of the formula: , of R² is independently unsubstituted alkyl, unsubstituted alkenyl, or unsubstituted alkynyl. In some embodiments, the phospholipids may be one or more of the phospholipids described in PCT Application No. PCT/US2018/037922. In some embodiments, a lipid nanoparticle comprises 5-25 mol% non-cationic lipid relative to the other lipid components. For example, a lipid nanoparticle may comprise 5-30 mol%, 5-15 mol%, 5-10 mol%, 10-25 mol%, 10-20 mol%, 10-25 mol%, 15-25 mol%, 15-20 mol%, 20-25 mol%, or 25-30 mol% non-cationic lipid. In some embodiments, a lipid nanoparticle comprises a 5 mol%, 10 mol%, 15 mol%, 20 mol%, 25 mol%, or 30 mol% non-cationic lipid. In some embodiments, a lipid nanoparticle comprises 5-25 mol% phospholipid relative to the other lipid components. For example, the lipid nanoparticle may comprise 5-30 mol%, 5-15 mol%, 5-10 mol%, 10-25 mol%, 10-20 mol%, 10-25 mol%, 15-25 153 Attorney Docket No.45817-0192WO1 / MTX1067.20 mol%, 15-20 mol%, 20-25 mol%, or 25-30 mol% phospholipid. In some embodiments, the lipid nanoparticle 5 mol%, 10 mol%, 15 mol%, 20 mol%, 25 mol%, or 30 mol% phospholipid lipid. Structural Lipids The lipid composition of a pharmaceutical composition disclosed herein can comprise one or more structural lipids. As used herein, the term “structural lipid” includes sterols and also to lipids containing sterol moieties. Incorporation of structural lipids in a lipid nanoparticle may help mitigate aggregation of other lipids in the particle. Structural lipids can be selected from the group including but not limited to, cholesterol, fecosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatidine, tomatine, ursolic acid, alpha-tocopherol, hopanoids, phytosterols, steroids, and mixtures thereof. In some embodiments, the structural lipid is a sterol. As defined herein, “sterols” are a subgroup of steroids consisting of steroid alcohols. In certain embodiments, the structural lipid is a steroid. In certain embodiments, the structural lipid is cholesterol. In certain embodiments, the structural lipid is an analog of cholesterol. In certain embodiments, the structural lipid is alpha-tocopherol. In some embodiments, the structural lipids may be one or more of the structural lipids described in U.S. Application No.16/493,814. In some embodiments, a lipid nanoparticle comprises 25-55 mol% structural lipid relative to the other lipid components. For example, a lipid nanoparticle may comprise 10- 55 mol%, 25-50 mol%, 25-45 mol%, 25-40 mol%, 25-35 mol%, 25-30 mol%, 30-55 mol%, 30-50 mol%, 30-45 mol%, 30-40 mol%, 30-35 mol%, 35-55 mol%, 35-50 mol%, 35-45 mol%, 35-40 mol%, 40-55 mol%, 40-50 mol%, 40-45 mol%, 45-55 mol%, 45-50 mol%, or 50-55 mol% structural lipid. In some embodiments, a lipid nanoparticle comprises 10 mol%, 15 mol%, 20 mol%, 25 mol%, 30 mol%, 35 mol%, 40 mol%, 45 mol%, 50 mol%, or 55 mol% structural lipid. 154 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, a lipid nanoparticle comprises 30-45 mol% sterol, optionally 35-40 mol%, for example, 30-31 mol%, 31-32 mol%, 32-33 mol%, 33-34 mol%, 35-35 mol%, 35-36 mol%, 36-37 mol%, 38-38 mol%, 38-39 mol%, or 39-40 mol%. In some embodiments, a lipid nanoparticle comprises 25-55 mol% sterol. For example, a lipid nanoparticle may comprise 25-50 mol%, 25-45 mol%, 25-40 mol%, 25- 35 mol%, 25-30 mol%, 30-55 mol%, 30-50 mol%, 30-45 mol%, 30-40 mol%, 30-35 mol%, 35-55 mol%, 35-50 mol%, 35-45 mol%, 35-40 mol%, 40-55 mol%, 40-50 mol%, 40-45 mol%, 45-55 mol%, 45-50 mol%, or 50-55 mol% sterol. In some embodiments, a lipid nanoparticle comprises 25 mol%, 30 mol%, 35 mol%, 40 mol%, 45 mol%, 50 mol%, or 55 mol% sterol. In some embodiments, a lipid nanoparticle comprises 35-40 mol% cholesterol. For example, a lipid nanoparticle may comprise 35, 35.5, 36, 36.5, 37, 37.5, 38, 38.5, 39, 39.5, or 40 mol% cholesterol. Polyethylene Glycol (PEG)-Lipids The lipid composition of a pharmaceutical composition disclosed herein can comprise one or more polyethylene glycol (PEG) lipids. As used herein, the term “PEG-lipid” or “PEG-modified lipid” refers to polyethylene glycol (PEG)-modified lipids. Non-limiting examples of PEG-lipids include PEG-modified phosphatidylethanolamine and phosphatidic acid, PEG-ceramide conjugates (e.g., PEG-CerC14 or PEG-CerC20), PEG-modified dialkylamines, and PEG- modified 1,2-diacyloxypropan-3-amines. Such lipids are also referred to as PEGylated lipids. For example, a PEG lipid can be PEG-c-DOMG, PEG-DMG, PEG-DLPE, PEG-DMPE, PEG-DPPC, or a PEG-DSPE lipid. In some embodiments, the PEG-lipid includes, but not limited to 1,2-dimyristoyl- sn-glycerol methoxypolyethylene glycol (PEG-DMG), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[amino(polyethylene glycol)] (PEG-DSPE), PEG-disteryl glycerol (PEG-DSG), PEG-dipalmetoleyl, PEG-dioleyl, PEG-distearyl, PEG- 155 Attorney Docket No.45817-0192WO1 / MTX1067.20 diacylglycamide (PEG-DAG), PEG-dipalmitoyl phosphatidylethanolamine (PEG-DPPE), or PEG-l,2-dimyristyloxlpropyl-3-amine (PEG-c-DMA). In some embodiments, the PEG-lipid is selected from the group consisting of a PEG-modified phosphatidylethanolamine, a PEG-modified phosphatidic acid, a PEG- modified ceramide, a PEG-modified dialkylamine, a PEG-modified diacylglycerol, a PEG-modified dialkylglycerol, and mixtures thereof. In some embodiments, the PEG- modified lipid is PEG-DMG, PEG-c-DOMG (also referred to as PEG-DOMG), PEG- DSG, and/or PEG-DPG. In some embodiments, the lipid moiety of the PEG-lipids includes those having lengths of from about C₁₄ to about C₂₂, preferably from about C₁₄ to about C₁₆. In some embodiments, a PEG moiety, for example an mPEG-NH2, has a size of about 1000, 2000, 5000, 10,000, 15,000 or 20,000 daltons. In some embodiments, the PEG-lipid is PEG_2k- DMG. In some embodiments, a lipid nanoparticles described herein can comprise a PEG lipid which is a non-diffusible PEG. Non-limiting examples of non-diffusible PEGs include PEG-DSG and PEG-DSPE. PEG-lipids are known in the art, such as those described in U.S. Patent No. 8158601 and International Publ. No. WO 2015/130584 A2, which are incorporated herein by reference in their entirety. In general, some of the other lipid components (e.g., PEG lipids) of various formulae described herein may be synthesized as described International Patent Application No. PCT/US2016/000129, filed December 10, 2016, entitled “Compositions and Methods for Delivery of Therapeutic Agents,” which is incorporated by reference in its entirety. The lipid component of a lipid nanoparticle composition may include one or more molecules comprising polyethylene glycol, such as PEG or PEG-modified lipids. Such species may be alternately referred to as PEGylated lipids. A PEG lipid is a lipid modified with polyethylene glycol. A PEG lipid may be selected from the non-limiting group including PEG-modified phosphatidylethanolamines, PEG-modified phosphatidic 156 Attorney Docket No.45817-0192WO1 / MTX1067.20 acids, PEG-modified ceramides, PEG-modified dialkylamines, PEG-modified diacylglycerols, PEG-modified dialkylglycerols, and mixtures thereof. For example, a PEG lipid may be PEG-c-DOMG, PEG-DMG, PEG-DLPE, PEG-DMPE, PEG-DPPC, or a PEG-DSPE lipid. In some embodiments the PEG-modified lipids are a modified form of PEG DMG. PEG-DMG has the following structure: can be PEGylated lipids described in International Publication No. WO2012099755, the contents of which is herein incorporated by reference in its entirety. Any of these exemplary PEG lipids described herein may be modified to comprise a hydroxyl group on the PEG chain. In certain embodiments, the PEG lipid is a PEG-OH lipid. As generally defined herein, a “PEG-OH lipid” (also referred to herein as “hydroxy- PEGylated lipid”) is a PEGylated lipid having one or more hydroxyl (–OH) groups on the lipid. In certain embodiments, the PEG-OH lipid includes one or more hydroxyl groups on the PEG chain. In certain embodiments, a PEG-OH or hydroxy-PEGylated lipid comprises an –OH group at the terminus of the PEG chain. Each possibility represents a separate embodiment of the present disclosure. In certain embodiments, a PEG lipid useful in the present disclosure is a compound of Formula (X): , or R³ is –OR^O; R^O is hydrogen, optionally substituted alkyl, or an oxygen protecting group; r is an integer between 1 and 100, inclusive; 157 Attorney Docket No.45817-0192WO1 / MTX1067.20 L¹ is optionally substituted C1-10 alkylene, wherein at least one methylene of the optionally substituted C_1-10 alkylene is independently replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, O, N(R^N), S, C(O), C(O)N(R^N), NR^NC(O), C(O)O, OC(O), OC(O)O, OC(O)N(R^N), NR^NC(O)O, or NR^NC(O)N(R^N); D is a moiety obtained by click chemistry or a moiety cleavable under physiological conditions; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; A is of the ; each instance of L² substituted C_1-6 alkylene, wherein one methylene unit of the optionally substituted C_1-6 alkylene is optionally replaced with O, N(R^N), S, C(O), C(O)N(R^N), NR^NC(O), C(O)O, OC(O), - OC(O)O, OC(O)N(R^N), NR^NC(O)O, or NR^NC(O)N(R^N); each instance of R² is independently optionally substituted C_1-30 alkyl, optionally substituted C1-30 alkenyl, or optionally substituted C1-30 alkynyl; optionally wherein one or more methylene units of R² are independently replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, N(R^N), O, S, C(O), C(O)N(R^N), NR^NC(O), - NR^NC(O)N(R^N), C(O)O, OC(O), OC(O)O, OC(O)N(R^N), NR^NC(O)O, C(O)S, SC(O), - C(=NR^N), C(=NR^N)N(R^N), NR^NC(=NR^N), NR^NC(=NR^N)N(R^N), C(S), C(S)N(R^N), - NR^NC(S), NR^NC(S)N(R^N), S(O) , OS(O), S(O)O, OS(O)O, OS(O)₂, S(O)₂O, OS(O)₂O, N(R^N)S(O), S(O)N(R^N), N(R^N)S(O)N(R^N), OS(O)N(R^N), N(R^N)S(O)O, S(O)2, - N(R^N)S(O)₂, S(O)₂N(R^N), N(R^N)S(O)₂N(R^N), OS(O)₂N(R^N), or N(R^N)S(O)₂O; each instance of R^N is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group; Ring B is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and p is 1 or 2. 158 Attorney Docket No.45817-0192WO1 / MTX1067.20 In certain embodiments, the compound of Formula (X) is a PEG-OH lipid (i.e., R³ is –OR^O, and R^O is hydrogen). In certain embodiments, the compound of Formula (X) is of Formula (X-OH): (X-OH), or a In certain embodiments, a PEG lipid useful in the present disclosure is a PEGylated fatty acid. In certain embodiments, a PEG lipid useful in the present disclosure is a compound of Formula (XI). Provided herein are compounds of Formula (XI): (XI), or a R³ is–OR^O; R^O is hydrogen, optionally substituted alkyl or an oxygen protecting group; r is an integer between 1 and 100, inclusive; R⁵ is optionally substituted C10-40 alkyl, optionally substituted C10-40 alkenyl, or optionally substituted C_10-40 alkynyl; and optionally one or more methylene groups of R⁵ are replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, - N(R^N), O, S, C(O), C(O)N(R^N), NR^NC(O), NR^NC(O)N(R^N), C(O)O, OC(O), OC(O)O, - O, a nitrogen protecting group. In certain embodiments, the compound of Formula (XI) is of Formula (XI-OH): 159 Attorney Docket No.45817-0192WO1 / MTX1067.20 , or a r is 40-50. In yet of Formula (XI) is: . In some embodiments, the compound of Formula (XI) is . disclosed herein does not comprise a PEG-lipid. In some embodiments, the PEG-lipids may be one or more of the PEG lipids described in U.S. Application No. US15/674,872. In some embodiments, a lipid nanoparticle comprises 0.5-15 mol% PEG lipid relative to the other lipid components. For example, a lipid nanoparticle may comprise 0.5-10 mol%, 0.5-5 mol%, 1-15 mol%, 1-10 mol%, 1-5 mol%, 2-15 mol%, 2-10 mol%, 2-5 mol%, 5-15 mol%, 5-10 mol%, or 10-15 mol% PEG lipid. In some embodiments, a lipid nanoparticle comprises 0.5 mol%, 1 mol%, 2 mol%, 3 mol%, 4 mol%, 5 mol%, 6 mol%, 7 mol%, 8 mol%, 9 mol%, 10 mol%, 11 mol%, 12 mol%, 13 mol%, 14 mol%, or 15 mol% PEG- lipid. In some embodiments, a lipid nanoparticle comprises 1-5% PEG-modified lipid, optionally 1-3 mol%, for example, 1.5 to 2.5 mol%, 1-2 mol%, 2-3 mol%, 3-4 mol%, or 4-5 mol%. In some embodiments, a lipid nanoparticle comprises 0.5-15 mol% PEG- modified lipid. For example, a lipid nanoparticle may comprise 0.5-10 mol%, 0.5-5 mol%, 1-15 mol%, 1-10 mol%, 1-5 mol%, 2-15 mol%, 2-10 mol%, 2-5 mol%, 5-15 mol%, 5-10 mol%, or 10-15 mol%. In some embodiments, a lipid nanoparticle comprises 0.5 mol%, 1 mol%, 2 mol%, 3 mol%, 4 mol%, 5 mol%, 6 mol%, 7 mol%, 8 mol%, 9 160 Attorney Docket No.45817-0192WO1 / MTX1067.20 mol%, 10 mol%, 11 mol%, 12 mol%, 13 mol%, 14 mol%, or 15 mol% PEG-modified lipid. Some embodiments comprise adding PEG to a composition comprising an LNP encapsulating a nucleic acid (e.g., which already includes PEG in the amounts listed above). Without being bound by theory, it is believed that spiking an LNP composition with additional PEG can provide benefits during lyophilization. Thus, some embodiments, comprise adding additional PEG as compared to an amount used for a non- lyophilized LNP composition. In embodiments comprise adding about 0.5mo% or more PEG to an LNP composition, such as about 1mol%, about 1.5mol%, about 2mol%, about 2.5mol%, about 3mol%, about 3.5mol%, about 4mol%, about 5mol%, or more after formation of an LNP composition (e.g., which already contains PEG in amount listed elsewhere herein). In some embodiments, a lipid nanoparticle comprises 20-60 mol% ionizable amino lipid, 5-25 mol% non-cationic lipid, 25-55 mol% sterol, and 0.5-15 mol% PEG- modified lipid. In some embodiments, an LNP of the disclosure comprises an ionizable amino lipid of Compound 1, wherein the non-cationic lipid is DSPC, the structural lipid that is cholesterol, and the PEG lipid is DMG-PEG. In some embodiments, an LNP of the present disclosure comprises an ionizable amino lipid of any of Formula VI, VII or VIII, a phospholipid comprising DSPC, a structural lipid, and a PEG lipid comprising PEG-DMG. In some embodiments, an LNP of the present disclosure comprises an ionizable amino lipid of any of Formula VI, VII or VIII, a phospholipid comprising DSPC, a structural lipid, and a PEG lipid comprising a compound having Formula XI. In some embodiments, an LNP of the present disclosure comprises an ionizable amino lipid of Formula VI, VII or VIII, a phospholipid comprising a compound having Formula VIII, a structural lipid, and the PEG lipid comprising a compound having Formula X or XI. 161 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, an LNP of the present disclosure comprises an ionizable amino lipid of Formula VI, VII or VIII, a phospholipid comprising a compound having Formula IX, a structural lipid, and the PEG lipid comprising a compound having Formula X or XI. In some embodiments, an LNP of the present disclosure comprises an ionizable amino lipid of Formula VI, VII or VIII, a phospholipid having Formula IX, a structural lipid, and a PEG lipid comprising a compound having Formula XI. In some embodiments, a lipid nanoparticle comprises 49 mol% ionizable amino lipid, 10 mol% DSPC, 38.5 mol% cholesterol, and 2.5 mol% DMG-PEG. In some embodiments, a lipid nanoparticle comprises 49 mol% ionizable amino lipid, 11 mol% DSPC, 38.5 mol% cholesterol, and 1.5 mol% DMG-PEG. In some embodiments, a lipid nanoparticle comprises 48 mol% ionizable amino lipid, 11 mol% DSPC, 38.5 mol% cholesterol, and 2.5 mol% DMG-PEG. In some embodiments, an LNP of the present disclosure comprises an N:P ratio of from about 2:1 to about 30:1. In some embodiments, an LNP of the present disclosure comprises an N:P ratio of about 6:1. In some embodiments, an LNP of the present disclosure comprises an N:P ratio of about 3:1, 4:1, or 5:1. In some embodiments, an LNP of the present disclosure comprises a wt/wt ratio of the ionizable amino lipid component to the RNA of from about 10:1 to about 100:1. In some embodiments, an LNP of the present disclosure comprises a wt/wt ratio of the ionizable amino lipid component to the RNA of about 20:1. In some embodiments, an LNP of the present disclosure comprises a wt/wt ratio of the ionizable amino lipid component to the RNA of about 10:1. Some embodiments comprise a composition having one or more LNPs having a diameter of about 150 nm or less, such as about 140 nm, 130 nm, 120 nm, 110 nm, 100 nm, 90 nm, 80 nm, 70 nm, 60 nm, 50 nm, 40 nm, 30 nm, or 20 nm or less. Some embodiments comprise a composition having a mean LNP diameter of about 150 nm or 162 Attorney Docket No.45817-0192WO1 / MTX1067.20 less, such as about 140 nm, 130 nm, 120 nm, 110 nm, 100 nm, 90 nm, 80 nm, 70 nm, 60 nm, 50 nm, 40 nm, 30 nm, or 20 nm or less. In some embodiments, the composition has a mean LNP diameter from about 30nm to about 150nm, or a mean diameter from about 60nm to about 120nm. AN LNP may comprise or one or more types of lipids, including but not limited to amino lipids (e.g., ionizable amino lipids), neutral lipids, non-cationic lipids, charged lipids, PEG-modified lipids, phospholipids, structural lipids and sterols. In some embodiments, an LNP may further comprise one or more cargo molecules, including but not limited to nucleic acids (e.g., mRNA, plasmid DNA, DNA or RNA oligonucleotides, siRNA, shRNA, snRNA, snoRNA, lncRNA, etc.), small molecules, proteins and peptides. In some embodiments, the composition comprises a liposome. A liposome is a lipid particle comprising lipids arranged into one or more concentric lipid bilayers around a central region. The central region of a liposome may comprise an aqueous solution, suspension, or other aqueous composition. In some embodiments, a lipid nanoparticle may comprise two or more components (e.g., amino lipid and nucleic acid, PEG-lipid, phospholipid, structural lipid). For instance, a lipid nanoparticle may comprise an amino lipid and a nucleic acid. Compositions comprising lipid nanoparticles, such as those described herein, may be used for a wide variety of applications, including the stealth delivery of mRNA with minimal adverse innate immune response. Effective in vivo delivery of nucleic acids represents a continuing medical challenge. Exogenous nucleic acids (i.e., originating from outside of a cell or organism) are readily degraded in the body, e.g., by the immune system. Accordingly, effective delivery of nucleic acids to cells often requires the use of a particulate carrier (e.g., lipid nanoparticles). The particulate carrier should be formulated to have minimal particle aggregation, be relatively stable prior to intracellular delivery, effectively deliver nucleic acids intracellularly, and illicit no or minimal immune response. To achieve minimal particle aggregation and pre-delivery stability, many conventional particulate carriers 163 Attorney Docket No.45817-0192WO1 / MTX1067.20 have relied on the presence and/or concentration of certain components (e.g., PEG-lipid). However, it has been discovered that certain components may decrease the stability of encapsulated nucleic acids (e.g., mRNA molecules). The reduced stability may limit the broad applicability of the particulate carriers. As such, there remains a need for methods by which to improve the stability of nucleic acid (e.g., mRNA) encapsulated within lipid nanoparticles. In some embodiments, a lipid nanoparticles comprise one or more of ionizable molecules, polynucleotides, and optional components, such as structural lipids, sterols, neutral lipids, phospholipids and a molecule capable of reducing particle aggregation (e.g., polyethylene glycol (PEG), PEG-modified lipid), such as those described above. In some embodiments, an LNP described herein may include one or more ionizable molecules (e.g., amino lipids or ionizable lipids). The ionizable molecule may comprise a charged group and may have a certain pKa. In certain embodiments, the pKa of the ionizable molecule may be greater than or equal to about 6, greater than or equal to about 6.2, greater than or equal to about 6.5, greater than or equal to about 6.8, greater than or equal to about 7, greater than or equal to about 7.2, greater than or equal to about 7.5, greater than or equal to about 7.8, greater than or equal to about 8. In some embodiments, the pKa of the ionizable molecule may be less than or equal to about 10, less than or equal to about 9.8, less than or equal to about 9.5, less than or equal to about 9.2, less than or equal to about 9.0, less than or equal to about 8.8, or less than or equal to about 8.5. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 6 and less than or equal to about 8.5). Other ranges are also possible. In embodiments in which more than one type of ionizable molecule are present in a particle, each type of ionizable molecule may independently have a pKa in one or more of the ranges described above. In general, an ionizable molecule comprises one or more charged groups. In some embodiments, an ionizable molecule may be positively charged or negatively charged. For instance, an ionizable molecule may be positively charged. For example, an ionizable molecule may comprise an amine group. As used herein, the term “ionizable molecule” 164 Attorney Docket No.45817-0192WO1 / MTX1067.20 has its ordinary meaning in the art and may refer to a molecule or matrix comprising one or more charged moiety. As used herein, a “charged moiety” is a chemical moiety that carries a formal electronic charge, e.g., monovalent (+1, or -1), divalent (+2, or -2), trivalent (+3, or -3), etc. The charged moiety may be anionic (i.e., negatively charged) or cationic (i.e., positively charged). Examples of positively-charged moieties include amine groups (e.g., primary, secondary, and/or tertiary amines), ammonium groups, pyridinium group, guanidine groups, and imidizolium groups. In a particular embodiment, the charged moieties comprise amine groups. Examples of negatively-charged groups or precursors thereof, include carboxylate groups, sulfonate groups, sulfate groups, phosphonate groups, phosphate groups, hydroxyl groups, and the like. The charge of the charged moiety may vary, in some cases, with the environmental conditions, for example, changes in pH may alter the charge of the moiety, and/or cause the moiety to become charged or uncharged. In general, the charge density of the molecule and/or matrix may be selected as desired. In some cases, an ionizable molecule (e.g., an amino lipid or ionizable lipid) may include one or more precursor moieties that can be converted to charged moieties. For instance, the ionizable molecule may include a neutral moiety that can be hydrolyzed to form a charged moiety, such as those described above. As a non-limiting specific example, the molecule or matrix may include an amide, which can be hydrolyzed to form an amine, respectively. Those of ordinary skill in the art will be able to determine whether a given chemical moiety carries a formal electronic charge (for example, by inspection, pH titration, ionic conductivity measurements, etc.), and/or whether a given chemical moiety can be reacted (e.g., hydrolyzed) to form a chemical moiety that carries a formal electronic charge. The ionizable molecule (e.g., amino lipid or ionizable lipid) may have any suitable molecular weight. In certain embodiments, the molecular weight of an ionizable molecule is less than or equal to about 2,500 g/mol, less than or equal to about 2,000 g/mol, less than or equal to about 1,500 g/mol, less than or equal to about 1,250 g/mol, less than or equal to about 1,000 g/mol, less than or equal to about 900 g/mol, less than or 165 Attorney Docket No.45817-0192WO1 / MTX1067.20 equal to about 800 g/mol, less than or equal to about 700 g/mol, less than or equal to about 600 g/mol, less than or equal to about 500 g/mol, less than or equal to about 400 g/mol, less than or equal to about 300 g/mol, less than or equal to about 200 g/mol, or less than or equal to about 100 g/mol. In some instances, the molecular weight of an ionizable molecule is greater than or equal to about 100 g/mol, greater than or equal to about 200 g/mol, greater than or equal to about 300 g/mol, greater than or equal to about 400 g/mol, greater than or equal to about 500 g/mol, greater than or equal to about 600 g/mol, greater than or equal to about 700 g/mol, greater than or equal to about 1000 g/mol, greater than or equal to about 1,250 g/mol, greater than or equal to about 1,500 g/mol, greater than or equal to about 1,750 g/mol, greater than or equal to about 2,000 g/mol, or greater than or equal to about 2,250 g/mol. Combinations of the above ranges (e.g., at least about 200 g/mol and less than or equal to about 2,500 g/mol) are also possible. In embodiments in which more than one type of ionizable molecules are present in a particle, each type of ionizable molecule may independently have a molecular weight in one or more of the ranges described above. In some embodiments, the percentage (e.g., by weight, or by mole) of a single type of ionizable molecule (e.g., amino lipid or ionizable lipid) and/or of all the ionizable molecules within a particle may be greater than or equal to about 15%, greater than or equal to about 16%, greater than or equal to about 17%, greater than or equal to about 18%, greater than or equal to about 19%, greater than or equal to about 20%, greater than or equal to about 21%, greater than or equal to about 22%, greater than or equal to about 23%, greater than or equal to about 24%, greater than or equal to about 25%, greater than or equal to about 30%, greater than or equal to about 35%, greater than or equal to about 40%, greater than or equal to about 42%, greater than or equal to about 45%, greater than or equal to about 48%, greater than or equal to about 50%, greater than or equal to about 52%, greater than or equal to about 55%, greater than or equal to about 58%, greater than or equal to about 60%, greater than or equal to about 62%, greater than or equal to about 65%, or greater than or equal to about 68%. In some instances, the percentage (e.g., by weight, or by mole) may be less than or equal to about 70%, less than or equal to about 166 Attorney Docket No.45817-0192WO1 / MTX1067.20 68%, less than or equal to about 65%, less than or equal to about 62%, less than or equal to about 60%, less than or equal to about 58%, less than or equal to about 55%, less than or equal to about 52%, less than or equal to about 50%, or less than or equal to about 48%. Combinations of the above referenced ranges are also possible (e.g., greater than or equal to 20% and less than or equal to about 60%, greater than or equal to 40% and less than or equal to about 55%, etc.). In embodiments in which more than one type of ionizable molecule is present in a particle, each type of ionizable molecule may independently have a percentage (e.g., by weight, or by mole) in one or more of the ranges described above. The percentage (e.g., by weight, or by mole) may be determined by extracting the ionizable molecule(s) from the dried particles using, e.g., organic solvents, and measuring the quantity of the agent using high pressure liquid chromatography (i.e., HPLC), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), or mass spectrometry (MS). Those of ordinary skill in the art would be knowledgeable of techniques to determine the quantity of a component using the above-referenced techniques. For example, HPLC may be used to quantify the amount of a component, by, e.g., comparing the area under the curve of a HPLC chromatogram to a standard curve. It should be understood that the terms “charged” or “charged moiety” does not refer to a “partial negative charge" or “partial positive charge" on a molecule. The terms “partial negative charge" and “partial positive charge" are given their ordinary meaning in the art. A “partial negative charge" may result when a functional group comprises a bond that becomes polarized such that electron density is pulled toward one atom of the bond, creating a partial negative charge on the atom. Those of ordinary skill in the art will, in general, recognize bonds that can become polarized in this way. According to the disclosures herein, a lipid composition may comprise one or more lipids as described herein. Such lipids may include those useful in the preparation of lipid nanoparticle formulations as described above or as known in the art. 167 Attorney Docket No.45817-0192WO1 / MTX1067.20 Multivalent Vaccines The compositions, as provided herein, include multiple RNAs (e.g., mRNAs) encoding two or more antigens. In some embodiments, composition includes an mRNA or multiple RNAs (e.g., mRNAs) encoding two or more HBV proteins. In some embodiments, the mRNA may encode 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, or more HBV proteins. In some embodiments, the mRNA may encode 3 or more HBV proteins. In some embodiments, the mRNA may encode 4 or more HBV proteins. In some embodiments, two or more different mRNA encoding antigens may be formulated in the same lipid nanoparticle. In other embodiments, two or more different mRNA encoding antigens may be formulated in separate lipid nanoparticles (each mRNA formulated in a single lipid nanoparticle). Lipid nanoparticles may then be combined and administered as a single vaccine composition (e.g., comprising multiple RNAs (e.g., mRNAs) encoding multiple antigens) or may be administered separately. Multivalent mRNAs are typically produced by transcribing using in vitro transcription one mRNA at a time, purifying each mRNA, and then mixing the purified mRNA together prior to formulation. In some embodiments, the vaccine compositions provided herein include a first mRNA encoding an HBV envelope antigen or a variant thereof, a second mRNA encoding an HBV core protein or a variant thereof, a third mRNA encoding an HBV polymerase protein or a variant thereof. In some embodiments, the vaccine compositions provided herein include a first mRNA encoding an HBV PreS1/S2 envelope antigen comprising a lumazine synthase domain, a second mRNA encoding an HBV core protein or a variant thereof, a third mRNA encoding an HBV polymerase protein or a variant thereof. In some embodiments, the vaccine compositions provided herein include a first mRNA encoding an HBV small envelope antigen or a variant thereof, a second mRNA encoding an HBV core protein or a variant thereof, a third mRNA encoding an HBV polymerase protein or a variant thereof. 168 Attorney Docket No.45817-0192WO1 / MTX1067.20 Pharmaceutical Formulations Provided herein are compositions (e.g., pharmaceutical compositions, such as vaccines), methods, kits and reagents for prevention of HBV and other conditions directly or indirectly cause by HBV infection in humans and other mammals, for example. The compositions provided herein can be used as a prophylactic agent to prevent an HBV infection, and thus HBV, cause by an HBV infection. In some embodiments, the compositions containing mRNA as described herein can be administered to a subject (e.g., a mammalian subject, such as a human subject), and the mRNA are translated in vivo to produce an antigenic polypeptide (antigen). An “effective amount” of a composition (e.g., comprising mRNA) is based, at least in part, on the target tissue, target cell type, means of administration, physical characteristics of the mRNA (e.g., length, nucleotide composition, and/or extent of modified nucleosides), other components of the vaccine, and other determinants, such as age, body weight, height, sex and general health of the subject. Typically, an effective amount of a composition provides an induced or boosted immune response as a function of antigen production in the cells of the subject. In some embodiments, an effective amount of the composition containing mRNA having at least one chemical modification are more efficient than a composition containing a corresponding unmodified polynucleotide encoding the same antigen or a peptide antigen. Increased antigen production may be demonstrated by increased cell transfection (the percentage of cells transfected with the mRNA vaccine), increased protein translation and/or expression from the polynucleotide, decreased nucleic acid degradation (as demonstrated, for example, by increased duration of protein translation from a modified polynucleotide), or altered antigen specific immune response of the host cell. The term "pharmaceutical composition" refers to the combination of an active agent (e.g., mRNA) with a carrier (e.g., lipid composition, e.g., LNP)), inert or active, making the composition especially suitable for prophylactic use in vivo or ex vivo. A "pharmaceutically acceptable carrier," after administered to or upon a subject, does not cause undesirable physiological effects. The carrier in the pharmaceutical composition 169 Attorney Docket No.45817-0192WO1 / MTX1067.20 must be "acceptable" also in the sense that it is compatible with the active ingredient and can be capable of stabilizing it. One or more solubilizing agents can be utilized as pharmaceutical carriers for delivery of an active agent. Examples of a pharmaceutically acceptable carrier include, but are not limited to, biocompatible vehicles, adjuvants, additives, and diluents to achieve a composition usable as a dosage form. Examples of other carriers include colloidal silicon oxide, magnesium stearate, cellulose, and sodium lauryl sulfate. Additional suitable pharmaceutical carriers and diluents, as well as pharmaceutical necessities for their use, are described in Remington's Pharmaceutical Sciences. In some embodiments, the compositions (comprising polynucleotides and their encoded polypeptides) in accordance with the present disclosure may be used for the prevention of an HBV infection. A composition may be administered prophylactically as part of an active immunization scheme to healthy individuals or early in infection during the incubation phase. In some embodiments, the amount of mRNA provided to a cell, a tissue or a subject may be an amount effective for immune prophylaxis. A composition may be administered with other prophylactic or therapeutic compounds. As a non-limiting example, a prophylactic or therapeutic compound may be an adjuvant or a booster. As used herein, when referring to a prophylactic composition, such as a vaccine, the term “booster” refers to an extra administration of the prophylactic (vaccine) composition. A booster (or booster vaccine) may be given after an earlier administration of the prophylactic composition. The time of administration between the initial administration of the prophylactic composition and the booster may be, but is not limited to, 12 hours, 1 day, 36 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 10 days, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 18 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, or more. In exemplary embodiments, the time of administration between the initial administration of the prophylactic composition and the booster may be, but is not limited to, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, or 6 months. As is described herein, the booster 170 Attorney Docket No.45817-0192WO1 / MTX1067.20 may comprise the same or different mRNA as compared to the earlier administration of the prophylactic composition. The booster, in some embodiments is monovalent (e.g., the mRNA encodes a single antigen). In some embodiments, the booster is multivalent (e.g., the mRNA encodes more than one antigen). In some embodiments, “administering” or “administration” means providing a material to a subject in a manner that is pharmacologically useful. In some embodiments, a composition disclosed herein is administered to a subject enterally. In some embodiments, an enteral administration of the composition is oral. In some embodiments, a composition disclosed herein is administered to the subject parenterally. In some embodiments, a composition disclosed herein is administered to a subject subcutaneously, intraocularly, intravitreally, subretinally, intravenously (IV), intracerebro-ventricularly, intramuscularly, intrathecally (IT), intracisternally, intraperitoneally, via inhalation, topically, or by direct injection to one or more cells, tissues, or organs. A composition may be utilized in various settings depending on the prevalence of the infection or the degree or level of unmet medical need. As a non-limiting example, the mRNA vaccines may be utilized to prevent HBV. mRNA vaccines have superior properties in that they produce much larger antibody titers, better neutralizing immunity, produce more durable immune responses, and/or produce responses earlier than commercially available vaccines. Provided herein are pharmaceutical compositions including mRNA and/or complexes optionally in combination with one or more pharmaceutically acceptable excipients. The mRNA may be formulated or administered alone or in conjunction with one or more other components. For example, a vaccine may comprise other components including, but not limited to, adjuvants. In some embodiments, a vaccine does not include an adjuvant (they are adjuvant free). 171 Attorney Docket No.45817-0192WO1 / MTX1067.20 An mRNA may be formulated or administered in combination with one or more pharmaceutically-acceptable excipients. In some embodiments, vaccines comprise at least one additional active substance, such as, for example, a therapeutically-active substance, a prophylactically-active substance, or a combination of both. Vaccine compositions may be sterile, pyrogen-free or both sterile and pyrogen-free. General considerations in the formulation and/or manufacture of pharmaceutical agents, such as vaccines, may be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety). In some embodiments, a vaccine is administered to humans, human patients or subjects. For the purposes of the present disclosure, the phrase “active ingredient” generally refers to the mRNA contained therein, for example, mRNA encoding HBV protein antigens. Formulations of the vaccines described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient (e.g., mRNA) into association with an excipient and/or one or more other accessory ingredients, and then, if necessary and/or desirable, dividing, shaping and/or packaging the product into a desired single- or multi-dose unit. Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition in accordance with the disclosure will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100%, e.g., between 0.5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient. In some embodiments, an mRNA is formulated using one or more excipients to: (1) increase stability; (2) increase cell transfection; (3) permit the sustained or delayed release (e.g., from a depot formulation); (4) alter the biodistribution (e.g., target to specific tissues or cell types); (5) increase the translation of encoded protein in vivo; 172 Attorney Docket No.45817-0192WO1 / MTX1067.20 and/or (6) alter the release profile of encoded protein (antigen) in vivo. In addition to traditional excipients such as any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, envelope active agents, isotonic agents, thickening or emulsifying agents, preservatives, excipients can include, without limitation, lipidoids, liposomes, lipid nanoparticles, polymers, lipoplexes, core-shell nanoparticles, peptides, proteins, cells transfected with the mRNA (e.g., for transplantation into a subject), hyaluronidase, nanoparticle mimics and combinations thereof. Combination therapy Some aspects of the present disclosure relate to administering subjects a composition of mRNA vaccine encoding one or more HBV proteins. In some embodiments, the mRNA vaccine is administered as a monotherapy or in combination with additional treatments. Standard of care treatment methods for HBV therapy include but are not limited to antiviral medications, nucleic acid therapies, liver transplantation, immune modulators such as interferon therapy, and combinations thereof such as combinations of antiviral medications and immune modulators. The choice of combination therapies depend on factors such as the stage of the disease, the presence of liver damage, viral load levels, and individual patient factors. Antiviral agents can be used to suppress HBV replication, reduce liver inflammation, and slow down disease progression. In some embodiments, the antiviral treatment is an inhibitor of viral replication. Non-limiting examples of inhibitors of viral replication include, but are not limited to Nucleos(t)ide analogues (NUCs). NUCs include but are not limited to Entecavir (Baraclude), Tenofovir disoproxil fumarate (TDF) (Viread), Tenofovir alafenamide (TAF) (Vemlidy, Lamivudine, and Telbivudine. Entecavir is a potent antiviral medication that effectively suppresses HBV replication by inhibiting reverse transcriptase, an enzyme essential for viral replication. Tenofovir is another potent NUC that works by inhibiting reverse transcriptase. It is available in both 173 Attorney Docket No.45817-0192WO1 / MTX1067.20 oral tablet and oral powder formulations. Tenofovir alafenamide is a newer formulation of tenofovir that has demonstrated similar efficacy to TDF but with potentially lower risks of renal and bone toxicity. Lamivudine is one of the older NUCs used for HBV treatment. It inhibits viral replication by interfering with the reverse transcriptase enzyme. Telbivudine is another NUC that inhibits HBV replication by targeting reverse transcriptase. The NUCs work by blocking the replication of HBV DNA, reducing viral load, and improving liver function. However, long-term treatment may be necessary to maintain viral suppression and prevent disease progression. Close monitoring of liver function and viral load is essential during treatment to assess the effectiveness of therapy and detect any potential resistance. Immune modulators are medications that help regulate the body's immune response. In the context of HBV infection, immune modulators may be used to enhance the immune system's ability to fight the virus or to suppress an overactive immune response that contributes to liver inflammation and damage. Immune modulators include but are not limited to Interferon-alpha (IFN-α), OX40 and OX40L, pegylated interferon- alpha, thymosin alpha-1, and cytokine-based therapies which can help regulate the body's immune response to the virus, potentially leading to viral clearance. IFN-α is a type of cytokine that helps regulate the immune response to viral infections. It can be administered as a subcutaneous injection and is typically used for a finite duration, often ranging from several months to a year. Interferon-alpha therapy can help suppress HBV replication, induce immune-mediated clearance of infected cells, and reduce the risk of liver cancer. Pegylated interferon-alpha has a longer half-life and is administered less frequently than conventional interferon-alpha. It is typically administered as a subcutaneous injection once weekly and has been shown to suppress HBV replication, promote seroconversion, and improve liver histology in some patients. OX40 (CD134) and its binding partner OX40-Ligand (OX40L) are members of the TNFR and TNF superfamilies that are involved immune modulation mediated by T cells, through T cell costimulation. The OX40/OX40L interaction controls the amount of pathogenic or 174 Attorney Docket No.45817-0192WO1 / MTX1067.20 protective effector T cells that are generated at the peak of the immune response and dictates the frequency of memory T cells that subsequently develop. Modulation of OX40/OX40L is an effective strategy for vaccination to promote naturally weak immune responses. Thymosin alpha-1 is a synthetic peptide that modulates immune function by stimulating the production and activity of T cells, natural killer cells, and other immune cells. Cytokine-based therapies include various cytokines, such as interleukin-2 (IL-2) and interleukin-12 (IL-12), that have been investigated as potential immune modulators for the treatment of chronic HBV infection. These cytokines can help regulate the immune response and enhance antiviral immunity. In another embodiment, the additional treatment is a nucleic acid therapy. In some embodiments, the nucleic acid therapy is an agent that reduce HBsAg. Nucleic acid therapy for treating HBV infection involves using nucleic acids, such as RNA or DNA, to target specific aspects of the HBV life cycle and suppress viral replication. Several nucleic acid-based approaches have been explored for HBV therapy, including RNA Interference (RNAi), Antisense Oligonucleotides (ASOs), and Gene Editing Technologies. RNAi is a natural cellular process that can be harnessed to silence specific genes, including those involved in viral replication. Small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) can be designed to target essential HBV genes, such as the HBsAg or HBV DNA polymerase genes. These siRNAs or shRNAs are delivered into hepatocytes to inhibit HBV replication and gene expression. ASOs are short, single- stranded nucleic acids that can bind to specific RNA sequences and modulate gene expression. ASOs can be designed to target viral RNA transcripts essential for HBV replication. By binding to these RNA molecules, ASOs can interfere with viral protein production or viral RNA stability, ultimately reducing viral replication. ASOs can target different regions of the HBV genome, including the pregenomic RNA (pgRNA), which serves as the template for viral DNA synthesis, as well as viral mRNAs encoding essential viral proteins. By inhibiting the expression of these viral RNA transcripts, ASOs can effectively suppress HBV replication and reduce viral load. Gene editing 175 Attorney Docket No.45817-0192WO1 / MTX1067.20 technologies, such as CRISPR/Cas9, have the potential to directly target and modify the HBV genome within infected cells. CRISPR/Cas9 can be programmed to cleave specific sequences within the HBV genome, leading to disruption of viral replication or elimination of viral DNA. Nucleic acid polymers (NAPs) are another form of HBV therapy. NAPs block the release of subviral particles from hepatocytes. NAPs include, for instance, REP 2006, the prototypic degenerate NAP [dN]40, containing TLR9-stimulatory CpG; REP 2055 a clinically active NAP with a sequence [dAdC]20 devoid of CpG content; REP 2139 and REP 2165. In another embodiment, the additional treatment is an immune stimulator. Non- limiting examples of immune stimulators include, but are not limited to, TLR 7/8 agonists; checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1); B and/or T cell vaccines; and/or cytokines (e.g., IFN-g). Another therapy is complementary and alternative medicine (CAM). CAM approaches for treating hepatitis B virus (HBV) infection may include various herbal remedies, dietary supplements, acupuncture, and traditional Chinese medicine. Herbal Remedies include for instance Silymarin (Milk thistle) and Licorice root. Dietary Supplements can include, for instance, Vitamin D and Omega-3 fatty acids. In other embodiments the compositions (e.g., vaccines) may be used for the prevention of an HBV infection in humans and other mammals. The compositions can be used as prophylactic agents, for example. In some embodiments, the compositions are used to provide prophylactic protection from an HBV infection. A subject may be any mammal, including non-human primate and human subjects. Typically, a subject is a human subject. In some embodiments, a composition is administered to a subject (e.g., a mammalian subject, such as a human subject) in an effective amount to induce an antigen-specific immune response. The RNA encoding the HBV protein is expressed and translated in vivo to produce the antigen, which then stimulates an immune response in the subject. 176 Attorney Docket No.45817-0192WO1 / MTX1067.20 Prophylactic protection from HBV disease or other condition cause directly or indirectly by HBV infection can be achieved following administration of a composition of the present disclosure. The compositions can be administered once, twice, three times, four times or more but it is likely sufficient to administer the composition once (optionally followed by a single booster). Dosing may need to be adjusted accordingly. A method of eliciting an immune response in a subject against an HBV protein (or multiple antigens) is provided in aspects of the present disclosure. In some embodiments, a method involves administering to the subject a vaccine comprising a mRNA having an open reading frame encoding an HBV protein (or multiple antigens), thereby inducing in the subject an immune response specific to the HBV protein (or multiple antigens), wherein anti-antigen antibody titer in the subject is increased following vaccination relative to anti-antigen antibody titer in a subject vaccinated with a prophylactically effective dose of a traditional vaccine against the antigen. An “anti-antigen antibody” is a serum antibody the binds specifically to the antigen. A prophylactically effective dose is an effective dose that prevents infection with the virus at a clinically acceptable level. In some embodiments, the effective dose is a dose listed in a package insert for the vaccine. A traditional vaccine, as used herein, refers to a vaccine other than the mRNA vaccines of the present disclosure. For instance, a traditional vaccine includes, but is not limited, to live microorganism vaccines, killed microorganism vaccines, subunit vaccines, protein antigen vaccines, DNA vaccines, virus like particle (VLP) vaccines, etc. In exemplary embodiments, a traditional vaccine is a vaccine that has achieved regulatory approval and/or is registered by a national drug regulatory body, for example the Food and Drug Administration (FDA) in the United States or the European Medicines Agency (EMA). A method of eliciting an immune response in a subject against HBV is provided in other aspects of the disclosure. The method involves administering to the subject a composition comprising an mRNA comprising an open reading frame encoding an HBV protein, thereby inducing in the subject an immune response specific to LD, wherein the immune response in the subject is equivalent to an immune response in a subject 177 Attorney Docket No.45817-0192WO1 / MTX1067.20 vaccinated with a traditional vaccine against HBV at 2 times to 100 times the dosage level relative to the composition. In some embodiments, the method involves administering to the subject a composition comprising an mRNA comprising an open reading frame encoding an HBV protein and in combination with siRNA/NUC and sustained viral suppression. In some embodiments, the immune response in the subject elicits a functional cure. As described herein, the term “functional cure” refers to baseline standard considered to be an effective treatment for HBV infection. In some embodiments the functional cure results in sustained undetectable HBsAg and HBV DNA in the subject and/or is sufficient to produce HBsAg seroconversion in the subject. The term “sustained” in this context refers to at least 1, 2, 3, 4, 5, 6 ,78, 9, 10, 11, or 12 months or at least 1, 2, 3, 4, 5, 6 ,78, 9, 10, 11, or 12 years. In some embodiments, the therapy resulting in a functional cure is sufficient such that the subject does not require lifelong treatment with current standard of care (e.g., treatment with siRNA/NUCs). In some embodiments, there is a reduced risk of progression to cirrhosis. In some embodiments, the clearance of acute infection is a model for productive immune responses in CHB. In some embodiments, the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at twice the dosage level relative to a composition of the present disclosure. In some embodiments, the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at three times the dosage level relative to a composition of the present disclosure. In some embodiments, the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at 4 times, 5 times, 10 times, 50 times, or 100 times the dosage level relative to a composition of the present disclosure. In some embodiments, the immune response in the subject is equivalent to an immune response in a subject vaccinated with a traditional vaccine at 10 times to 1000 times the dosage level relative to a composition of the present disclosure. In some embodiments, the immune response in the subject is equivalent to an 178 Attorney Docket No.45817-0192WO1 / MTX1067.20 immune response in a subject vaccinated with a traditional vaccine at 100 times to 1000 times the dosage level relative to a composition of the present disclosure. Other aspects the disclosure provide methods of eliciting an immune response in a subject against HBV by administering to the subject composition comprising an mRNA having an open reading frame encoding an HBV protein, thereby inducing in the subject an immune response specific to the HBV protein, wherein the immune response in the subject is induced 2 days to 10 weeks earlier relative to an immune response induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine against HBV. In some embodiments, the immune response in the subject is induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine at 2 times to 100 times the dosage level relative to a composition of the present disclosure. In some embodiments, the immune response in the subject is induced 2 days, 3 days, 1 week, 2 weeks, 3 weeks, 5 weeks, or 10 weeks earlier relative to an immune response induced in a subject vaccinated with a prophylactically effective dose of a traditional vaccine. Also provided herein are methods of eliciting an immune response in a subject against HBV by administering to the subject an mRNA having an open reading frame encoding at least one HBV protein, wherein the mRNA does not include a stabilization element, and wherein an adjuvant is not co-formulated or co-administered with the vaccine. A composition may be administered by any route that results in a prophylactically effective outcome. These include, but are not limited, to intradermal, intramuscular, intranasal, and/or subcutaneous administration. The present disclosure provides methods comprising administering mRNA vaccines to a subject in need thereof. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the disease, the particular composition, its mode of administration, its mode of activity, and the like. The mRNA is typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the mRNA may be decided by the 179 Attorney Docket No.45817-0192WO1 / MTX1067.20 attending physician within the scope of sound medical judgment. The specific prophylactically effective dose level for any particular patient will depend upon a variety of factors including the disorder being addressed and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. The effective amount of the mRNA (e.g., an effective dose), as provided herein, may be as low as 20 µg, administered for example as a single dose or as two 10 µg doses (e.g., a first effective vaccine dose and a second effective vaccine dose). In some embodiments, the first effective vaccine dose and the second effective vaccine dose are the same amount. In some embodiments, the first effective vaccine dose and the second effective vaccine dose are different amounts. In some embodiments, the effective amount is a total dose of 5 µg-30 µg, 5 µg -25 µg, 5 µg -20 µg, 5 µg -15 µg, 5 µg -10 µg, 10 µg - 30 µg, 10 µg -25 µg, 10 µg-20 µg, 10 µg -15 µg, 15 µg -30 µg, 15 µg -25 µg, 15 µg -20 µg, 20 µg -30 µg, 25 µg -30 µg, or 25 µg-300 µg. In some embodiments, the effective dose (e.g., effective amount) is at least 10 µg and less than 25 µg of the composition. In some embodiments, the effective dose (e.g., effective amount) is at least 5 µg and less than 25 µg of the composition. For example, the effective amount may be a total dose of 5 µg, 10 µg, 15 µg, 20 µg, 25 µg, 30 µg, 35 µg, 40 µg, 45 µg, 50 µg, 55 µg, 60 µg, 65 µg, 70 µg, 75 µg, 80 µg, 85 µg, 90 µg, 95 µg, 100 µg, 110 µg, 120 µg, 130 µg, 140 µg, 150 µg, 160 µg, 170 µg, 180 µg, 190 µg, 200 µg, 250 µg, or 300 µg. In some embodiments, the effective amount (e.g., effective dose) is a total dose of 10 μg. In some embodiments, the effective amount is a total dose of 20 μg (e.g., two 10 μg doses). In some embodiments, the effective amount is a total dose of 25 μg. In some embodiments, the effective amount is a total dose of 30 μg. In some embodiments, the effective amount is a total dose of 50 μg. In some embodiments, the effective amount is a total dose of 60 μg (e.g., two 30 μg doses). In some embodiments, the effective amount is a total dose of 75 180 Attorney Docket No.45817-0192WO1 / MTX1067.20 μg. In some embodiments, the effective amount is a total dose of 100 μg. In some embodiments, the effective amount is a total dose of 150 μg. In some embodiments, the effective amount is a total dose of 200 μg. In some embodiments, the effective amount is a total dose of 250 μg. In some embodiments, the effective amount is a total dose of 300 μg. The mRNA described herein can be formulated into a dosage form described herein, such as an intranasal, intratracheal, or injectable (e.g., intravenous, intraocular, intravitreal, intramuscular, intradermal, intracardiac, intraperitoneal, and subcutaneous). Vaccine Efficacy Some aspects of the present disclosure provide formulations of the compositions (e.g., RNA vaccines), wherein the mRNA is formulated in an effective amount to produce an antigen specific immune response in a subject (e.g., production of antibodies specific to an HBV antigen). “An effective amount” is a dose of the mRNA effective to produce an antigen-specific immune response. Also provided herein are methods of inducing an antigen-specific immune response in a subject. As used herein, an immune response to a vaccine of the present disclosure is the development in a subject of a humoral and/or a cellular immune response to a (one or more) HBV protein(s) encoded by the mRNA present in the vaccine. For purposes of the present disclosure, a “humoral” immune response refers to an immune response mediated by antibody molecules, including, e.g., secretory (IgA) or IgG molecules, while a “cellular” immune response is one mediated by T-lymphocytes (e.g., CD4+ helper and/or CD8+ T cells (e.g., CTLs) and/or other white blood cells. One important aspect of cellular immunity involves an antigen-specific response by cytolytic T-cells (CTLs). CTLs have specificity for peptide antigens that are presented in association with proteins encoded by the major histocompatibility complex (MHC) and expressed on the surfaces of cells. CTLs help induce and promote the destruction of intracellular microbes or the lysis of cells infected with such microbes. Another aspect of cellular immunity involves and antigen-specific response by helper T-cells. Helper T-cells act to help stimulate the 181 Attorney Docket No.45817-0192WO1 / MTX1067.20 function and focus the activity nonspecific effector cells against cells displaying peptide antigens in association with MHC molecules on their surface. A cellular immune response also leads to the production of cytokines, chemokines, and other such molecules produced by activated T-cells and/or other white blood cells including those derived from CD4+ and CD8+ T-cells. Humoral immune responses may be further divided into Th1 and Th2 responses, resulting the production of Th1-type cytokines and Th2-type cytokines, respectively. Th1-type cytokines tend to produce the proinflammatory responses responsible for killing intracellular parasites and for perpetuating autoimmune responses. The main Th1 cytokine is interferon gamma. Excessive proinflammatory responses (e.g., Th1-based responses), in some embodiments, can lead to uncontrolled tissue damage, and are counteracted by the Th2-type cytokines. The Th2-type cytokines include interleukins 4, 5, and 13, which are associated with the promotion of IgE and eosinophilic responses in atopy, and also interleukin-10, which is anti-inflammatory. In excess, Th2 responses will counteract the Th1 mediated microbicidal action. Accordingly, in some embodiments, the vaccines provided herein elicit a balanced Th1 and Th2 response. In some embodiments, administration of the vaccines provided herein may result in a Th17 response. T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17. Th17 cells maintain mucosal barriers and contribute to pathogen clearance at the mucosal surfaces. The Th17-type cytokines target innate immune cells and epithelial cells to produce G-CSF and Il-8, leading to neutrophil production and recruitment. In some embodiments, the compositions (e.g., vaccines) of the present disclosure produce a Th1 response. In some embodiments, the compositions (e.g., vaccines) of the present disclosure produce a Th2 response. In some embodiments, the compositions (e.g., vaccines) of the present disclosure produce a Th17 response. In some embodiments, the compositions (e.g., vaccines) of the present disclosure produce Th1 and Th2 responses, Th1 and Th17 responses, Th2 and Th17 responses, or Th1, Th2, and Th17 responses. In some embodiments, the antigen-specific immune response is characterized by measuring an anti-HBV antigen antibody titer produced in a subject administered a 182 Attorney Docket No.45817-0192WO1 / MTX1067.20 composition as provided herein. An antibody titer is a measurement of the amount of antibodies within a subject, for example, antibodies that are specific to a particular antigen or epitope of an antigen. Antibody titer is typically expressed as the inverse of the greatest dilution that provides a positive result. Enzyme-linked immunosorbent assay (ELISA) is a common assay for determining antibody titers, for example. A variety of serological tests can be used to measure antibody against encoded antigen of interest, for example, an HBV antigen. These tests include the hemagglutination-inhibition test, complement fixation test, fluorescent antibody test, enzyme-linked immunosorbent assay (ELISA), and plaque reduction neutralization test (PRNT). Each of these tests measures different antibody activities. In exemplary embodiments, A plaque reduction neutralization test, or PRNT (e.g., PRNT50 or PRNT90) is used as a serological correlate of protection. PRNT measures the biological parameter of in vitro virus neutralization and is the most serologically virus-specific test among certain classes of viruses, correlating well to serum levels of protection from virus infection. The basic design of the PRNT allows for virus-antibody interaction to occur in a test tube or microtiter plate, and then measuring antibody effects on viral infectivity by plating the mixture on virus-susceptible cells, preferably cells of mammalian origin. The cells are overlaid with a semi-solid media that restricts spread of progeny virus. Each virus that initiates a productive infection produces a localized area of infection (a plaque), that can be detected in a variety of ways. Plaques are counted and compared back to the starting concentration of virus to determine the percent reduction in total virus infectivity. In PRNT, the serum sample being tested is usually subjected to serial dilutions prior to mixing with a standardized amount of virus. The concentration of virus is held constant such that, when added to susceptible cells and overlaid with semi-solid media, individual plaques can be discerned and counted. In this way, PRNT end-point titers can be calculated for each serum sample at any selected percent reduction of virus activity. In functional assays intended to assess vaccinal immunogenicity, the serum sample dilution series for antibody titration should ideally start below the 183 Attorney Docket No.45817-0192WO1 / MTX1067.20 “seroprotective” threshold titer. Regarding HBV neutralizing antibodies, a seropositivity threshold of 1:10 can be considered a seroprotection threshold in certain embodiments. PRNT end-point titers are expressed as the reciprocal of the last serum dilution showing the desired percent reduction in plaque counts. The PRNT titer can be calculated based on a 50% or greater reduction in plaque counts (PRNT50). A PRNT50 titer is preferred over titers using higher cut-offs (e.g., PRNT90) for vaccine sera, providing more accurate results from the linear portion of the titration curve. There are several ways to calculate PRNT titers. The simplest and most widely used way to calculate titers is to count plaques and report the titer as the reciprocal of the last serum dilution to show >50% reduction of the input plaque count as based on the back-titration of input plaques. Use of curve fitting methods from several serum dilutions may permit calculation of a more precise result. There are a variety of computer analysis programs available for this (e.g., SPSS or GraphPad Prism). In some embodiments, an antibody titer is used to assess whether a subject has had an infection or to determine whether immunizations are required. In some embodiments, an antibody titer is used to determine the strength of an autoimmune response, to determine whether a booster immunization is needed, to determine whether a previous vaccine was effective, and to identify any recent or prior infections. In accordance with the present disclosure, an antibody titer may be used to determine the strength of an immune response induced in a subject by an RNA vaccine. In some embodiments, the anti-HBV antigen antibody titer produced in a subject is increased by at least 1 log relative to a control. For example, the anti-HBV antigen antibody titer produced in a subject may be increased by at least 1.5, at least 2, at least 2.5, or at least 3 log relative to a control. In some embodiments, the anti-HBV antigen antibody titer produced in the subject is increased by 1, 1.5, 2, 2.5 or 3 log relative to a control. In some embodiments, the anti-HBV antigen antibody titer produced in the subject is increased by 1-3 log relative to a control. For example, the anti-HBV antigen antibody titer produced in a subject may be increased by 1-1.5, 1-2, 1-2.5, 1-3, 1.5-2, 1.5- 2.5, 1.5-3, 2-2.5, 2-3, or 2.5-3 log relative to a control. 184 Attorney Docket No.45817-0192WO1 / MTX1067.20 In some embodiments, the anti-HBV antigen antibody titer produced in a subject is increased at least 2 times relative to a control. For example, the anti-HBV antigen antibody titer produced in a subject may be increased at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, or at least 10 times relative to a control. In some embodiments, the anti-HBV antigen antibody titer produced in the subject is increased 2, 3, 4, 5, 6, 7, 8, 9, or 10 times relative to a control. In some embodiments, the anti-HBV antigen antibody titer produced in a subject is increased 2-10 times relative to a control. For example, the anti-HBV antigen antibody titer produced in a subject may be increased 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6- 9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, or 9-10 times relative to a control. In some embodiments, an antigen-specific immune response is measured as a ratio of geometric mean titer (GMT), referred to as a geometric mean ratio (GMR), of serum neutralizing antibody titers to LD. A geometric mean titer (GMT) is the average antibody titer for a group of subjects calculated by multiplying all values and taking the nth root of the number, where n is the number of subjects with available data. A control, in some embodiments, is an anti-HBV antigen antibody titer produced in a subject who has not been administered an mRNA vaccine. In some embodiments, a control is an anti-HBV antigen antibody titer produced in a subject administered a recombinant or purified protein vaccine. Recombinant protein vaccines typically include protein antigens that either have been produced in a heterologous expression system (e.g., bacteria or yeast) or purified from large amounts of the pathogenic organism. In some embodiments, the ability of an mRNA vaccine to be effective is measured in a murine model. For example, a composition may be administered to a murine model and the murine model assayed for induction of neutralizing antibody titers. Viral challenge studies may also be used to assess the efficacy of a vaccine of the present disclosure. For example, a composition may be administered to a murine model, the murine model challenged with virus, and the murine model assayed for survival and/or 185 Attorney Docket No.45817-0192WO1 / MTX1067.20 immune response (e.g., neutralizing antibody response, T cell response (e.g., cytokine response)). In some embodiments, an effective amount of an mRNA vaccine is a dose that is reduced compared to the standard of care dose of a recombinant protein vaccine. A “standard of care,” as provided herein, refers to a medical prophylaxis guideline and can be general or specific. “Standard of care” specifies appropriate prophylaxis based on scientific evidence and collaboration between medical professionals involved in the prophylaxis of a given condition. It is the prophylactic process that a physician/ clinician should follow for a certain type of patient, illness or clinical circumstance. A “standard of care dose,” as provided herein, refers to the dose of a recombinant or purified protein vaccine, or a live attenuated or inactivated vaccine, or a VLP vaccine, that a physician/clinician or other medical professional would administer to a subject to prevent HBV infections or a related condition, while following the standard of care guideline for preventing HBV infection or a related condition. In some embodiments, the anti-HBV antigen antibody titer produced in a subject administered an effective amount of an composition is equivalent to the anti-HBV antigen antibody titer produced in a control subject administered a standard of care dose of a recombinant or purified protein vaccine, or a live attenuated or inactivated vaccine, or a VLP vaccine. Vaccine efficacy may be assessed using standard analyses (see, e.g., Weinberg et al., J Infect Dis.2010 Jun 1;201(11):1607-10). For example, vaccine efficacy may be measured by double-blind, randomized, clinical controlled trials. Vaccine efficacy may be expressed as a proportionate reduction in disease attack rate (AR) between the unvaccinated (ARU) and vaccinated (ARV) study cohorts and can be calculated from the relative risk (RR) of disease among the vaccinated group with use of the following formulas: Efficacy = (ARU – ARV)/ARU x 100; and Efficacy = (1-RR) x 100. 186 Attorney Docket No.45817-0192WO1 / MTX1067.20 Likewise, vaccine effectiveness may be assessed using standard analyses (see, e.g., Weinberg et al., J Infect Dis.2010 Jun 1;201(11):1607-10). Vaccine effectiveness is an assessment of how a vaccine (which may have already proven to have high vaccine efficacy) reduces disease in a population. This measure can assess the net balance of benefits and adverse effects of a vaccination program, not just the vaccine itself, under natural field conditions rather than in a controlled clinical trial. Vaccine effectiveness is proportional to vaccine efficacy (potency) but is also affected by how well target groups in the population are immunized, as well as by other non-vaccine-related factors that influence the ‘real-world’ outcomes of hospitalizations, ambulatory visits, or costs. For example, a retrospective case control analysis may be used, in which the rates of vaccination among a set of infected cases and appropriate controls are compared. Vaccine effectiveness may be expressed as a rate difference, with use of the odds ratio (OR) for developing infection despite vaccination: Effectiveness = (1 – OR) x 100. In some embodiments, efficacy of an mRNA vaccine is at least 60% relative to unvaccinated control subjects. For example, efficacy of the composition may be at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95%, at least 98%, or 100% relative to unvaccinated control subjects. Sterilizing Immunity. Sterilizing immunity refers to a unique immune status that prevents effective pathogen infection into the host. In some embodiments, the effective amount of a composition of the present disclosure is sufficient to provide sterilizing immunity in the subject for at least 1 year. For example, the effective amount of a composition of the present disclosure is sufficient to provide sterilizing immunity in the subject for at least 2 years, at least 3 years, at least 4 years, at least 5 years, at least 6 years, at least 7 years, at least 8 years, at least 9 years, at least 10 years, or more. In some embodiments, the effective amount of a composition of the present disclosure is sufficient to provide sterilizing immunity in the subject at an at least 5-fold lower dose relative to control. For example, the effective amount may be sufficient to provide 187 Attorney Docket No.45817-0192WO1 / MTX1067.20 sterilizing immunity in the subject at an at least 10-fold lower, 15-fold, or 20-fold lower dose relative to a control. Detectable Antigen. In some embodiments, the effective amount of a composition of the present disclosure is sufficient to produce detectable levels of HBV antigen as measured in serum of the subject at 1-72 hours post administration. Titer. An antibody titer is a measurement of the number of antibodies within a subject, for example, antibodies that are specific to a particular antigen (e.g., an anti-HBV antigen). Antibody titer is typically expressed as the inverse of the greatest dilution that provides a positive result. Enzyme-linked immunosorbent assay (ELISA) is a common assay for determining antibody titers, for example. In some embodiments, the effective amount of a composition of the present disclosure is sufficient to produce a 1,000-10,000 neutralizing antibody titer produced by neutralizing antibody against the specific antigen as measured in serum of the subject at 1-72 hours post administration. In some embodiments, the effective amount is sufficient to produce a 1,000-5,000 neutralizing antibody titer produced by neutralizing antibody against the specific antigen as measured in serum of the subject at 1-72 hours post administration. In some embodiments, the effective amount is sufficient to produce a 5,000-10,000 neutralizing antibody titer produced by neutralizing antibody against the specific antigen as measured in serum of the subject at 1-72 hours post administration. In some embodiments, the neutralizing antibody titer is at least 100 NT₅₀. For example, the neutralizing antibody titer may be at least 200, 300, 400, 500, 600, 700, 800, 900 or 1000 NT₅₀. In some embodiments, the neutralizing antibody titer is at least 10,000 NT₅₀. In some embodiments, the neutralizing antibody titer is at least 100 neutralizing units per milliliter (NU/mL). For example, the neutralizing antibody titer may be at least 200, 300, 400, 500, 600, 700, 800, 900 or 1000 NU/mL. In some embodiments, the neutralizing antibody titer is at least 10,000 NU/mL. In some embodiments, an anti-HBV antigen antibody titer produced in the subject is increased by at least 1 log relative to a control. For example, an anti-HBV 188 Attorney Docket No.45817-0192WO1 / MTX1067.20 antigen antibody titer produced in the subject may be increased by at least 2, 3, 4, 5, 6, 7, 8, 9 or 10 log relative to a control. In some embodiments, an anti-HBV antigen antibody titer produced in the subject is increased at least 2 times relative to a control. For example, an anti-HBV antigen antibody titer produced in the subject is increased by at least 3, 4, 5, 6, 7, 8, 9 or 10 times relative to a control. In some embodiments, a geometric mean, which is the nth root of the product of n numbers, is generally used to describe proportional growth. Geometric mean, in some embodiments, is used to characterize antibody titer produced in a subject. A control may be, for example, an unvaccinated subject, or a subject administered a live vaccine or a protein subunit vaccine. EXAMPLES According to the present disclosure, the manufacture of polynucleotides and/or parts or regions thereof may be accomplished utilizing the methods taught in International Publication WO2014/152027, entitled “Manufacturing Methods for Production of RNA Transcripts,” the content of which is incorporated herein by reference in its entirety. Purification methods may include those taught in International Publication WO2014/152030 and International Publication WO2014/152031, each of which is incorporated herein by reference in its entirety. Detection and characterization methods of the polynucleotides may be performed as taught in International Publication WO2014/144039, which is incorporated herein by reference in its entirety. Characterization of the polynucleotides of the disclosure may be accomplished using polynucleotide mapping, reverse transcriptase sequencing, charge distribution analysis, detection of RNA impurities, or any combination of two or more of the foregoing. “Characterizing” comprises determining the RNA transcript sequence, determining the purity of the RNA transcript, or determining the charge heterogeneity of 189 Attorney Docket No.45817-0192WO1 / MTX1067.20 the RNA transcript, for example. Such methods are taught in, for example, International Publication WO2014/144711 and International Publication WO2014/144767, the contents of each of which are incorporated herein by reference in their entirety. In experiments where a lipid nanoparticle (LNP) formulation was used, the formulation includes 0.5-15% PEG-modified lipid, 5-25% non-cationic lipid, 25-55% sterol, and 20-60% ionizable amino lipid. The PEG-modified lipid is 1,2 dimyristoyl-sn- glycerol, methoxypolyethyleneglycol (PEG2000 DMG), the non-cationic lipid is 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC), the sterol is cholesterol, and the ionizable amino . METHODS: Live Virus Neutralization Assay HepG2-NTCP Clone G4 cells were plated at 1.5 x 10⁵ cells/mL.1.5 x 10⁴ cells/well and left overnight at 37 C. Next, the media was replaced with pre-infection media. Pre-infection media contains DMEM, 3% FBS, and 2% DMSO. Cells were left overnight at 37 C. Infection media contains DMEM, 3% FBS, 2% DMSO and 4% PEG- 80000. The media was then incubated with HBV-D virus for one hour at room temperature. The mixture of HBV-D virus and media was added to cells for approximately 24 hours at 37 C. The cells were washed three times and replaced with fresh infection media. The fresh infection media contained DMEM, 3% FBS, 2% DMSO and 4% PEG-80000. After approximately six days at 37 C ELISA a readout of HBeAg was performed using two commercially available recombinant antibodies for HBe antigen, e6 as coating antibody and e13-HRP as a secondary antibody. HepG2-NTCP Cell Line Generation Three plasmids, psPAX2-GENScript-Industrial-Grade, pCAGGS-VSV-G-Kan- MK-8/5-#1, pLV-EF1a-(ACC)-NTCP-T2A-Puro-with-2-changes and Mirus LT1 were 190 Attorney Docket No.45817-0192WO1 / MTX1067.20 transfected with LentiX 293T cells for approximately 48 hours. Next, lentivirus containing VSV-G and NTCP were harvested from the supernatant. HepG2 cells were transduced with harvested lentivirus for approximately 72 hours. Next 8ug/mL puromycin selection media was added to generate HepG2-NTCP cells. Single-cell cloning dilutions were prepared and 10 single-cell clones were chosen to scale up and test in HBV neutralization. HepG2-NTCP clones were tested for dynamic range and HBV-D Neutralization. Cells were plated at a concentration of 1.5 x 10⁴ cells/well in Corning pre-coated collagen plates. The coating concentration was 2 ug/mL e6 coating. The clone having the highest dynamic range and highest NT50 from close with a dynamic range greater than 40 was selected. Example 1. HBV Envelope Antigen Immunogenicity Study A screen was conducted using vaccine compositions comprising lipid nanoparticles encapsulating an mRNA polynucleotides having an ORF encoding an HBV envelope antigen (Genotype A) to test the immunogenicity of the vaccine compositions. Additionally, the functional abilities of antibodies generated by vaccine composition administration was assessed using a neutralization assay. Antigen designs of immunogens encoded by the mRNA are indicated in Tables 3- 5. As shown in Tables 3-5, the antigens were variants of HBV envelope protein. Compositions in Groups 1 and 2 comprised mRNA polynucleotides having an ORF encoding HBV large envelope antigen with a N-terminal signal peptide and two alanine mutations at amino acid positions 190 and 198. Compositions in Groups 3 and 4 comprised mRNA polynucleotides having an ORF encoding the PreS1 and PreS2 domains with a N-terminal signal peptide, and HATM sequence. Compositions in Groups 5 and 6 comprised mRNA polynucleotides having an ORF encoding the PreS1 and PreS2 domains with a N-terminal signal peptide, and lumazine synthase. Compositions in Groups 7 and 8 comprised mRNA polynucleotides having an ORF encoding the PreS1 and PreS2 domains with a N-terminal signal peptide, and ferritin. Compositions in 191 Attorney Docket No.45817-0192WO1 / MTX1067.20 Groups 9 and 10 comprised mRNA polynucleotides having an ORF encoding the PreS1 domains with a N-terminal signal peptide, and ferritin. Compositions in Groups 11 and 12 are small envelope antigens delivered in a subviral particles (SVP). Groups 13 and 14 were administered SVPs containing Recombivax HB and adjuvated with alum (Merck Alum). Groups 15 and 16 were administered SVPs containing Heplisav-B and adjuvated with CpG oligonucleotides (Dynavax). Group 17 was administered PBS as a control. CB6F1 mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum samples were taken on Day 22 and Day 43. Spleen samples were taken on Day 43. Groups 1, 3, 5, 7, 9, 11 were administered a dose of 1 μg. Groups 2, 4, 6, 8, 10, 12 were administered a dose of 0.1 μg. Groups 13 and 15 were administered a dose of 0.5 μg. Groups 14 and 16 were administered a dose of 0.05 μg. Table 3: HBV envelope antigen construct design for FIGs.1A, 1B, and 1D Group ^{Composition Format Dose} _{N SEQ ID} _{# (μg)} NO: Attorney Docket No.45817-0192WO1 / MTX1067.20 13 RECOMBIVAX HB® (Merck SVP 0.5 8 - A_lum) Group Com SEQ ID NO: # position Dose (μg) Group # Composition Dose (μg) SEQ ID NO: 1 UL130 i P L S A 2Al 1 18 The total HBV-specific IgG levels were measured on Day 43. Compared to PBS treated mice, Groups 1, 3, 5, 7, and 9 showed enhanced production of HBV PreS1 and PreS1/S2 IgG (FIGs.1A-1B). Groups 8 and 9 showed enhanced production of HBV Small IgG (FIG.1C). Therefore, vaccine compositions comprising lipid nanoparticles encapsulating an mRNA polynucleotides having an ORF encoding an HBV envelope 193 Attorney Docket No.45817-0192WO1 / MTX1067.20 antigen demonstrate high induction of HBV-specific IgG. Also, compared to membrane- anchored, nanoparticle display of PreS1 or PreS1 and PreS2 elicits highest titer of PreS1 and PreS2 directed antibodies. Also, Small SVPs are highly immunogenic. The neutralization activity was measured on Day 43 using the Live Virus Neutralization Assay. Compared to positive control, A15, mRNA-encoding Small SVPs (Groups 11 and 12) elicited the highest neutralization, followed by PreS1 and PreS2 display by Lumazine Synthase (LuS) nanoparticles (Groups 5 and 6). Both mRNA- encoding Small SVPs (Groups 11 and 12) and PreS1 and PreS2 displayed by Lumazine Synthase (LuS) nanoparticles (Groups 5 and 6) quite surprisingly had higher neutralization activity than commercial vaccines (Groups 13-16) (FIG.1D). A competition ELISA assay was performed to assess elicitation of PreS1 specific antibodies from polyclonal immune sera using PreS1 monoclonal antibody Ma18/7. The results of the Ma18/7 competition showed the highest signal reduction in Group 5 (FIG. 1E). Ma18/7 signal reduction vs. PreS1 IgG correlation plots also showed that Group 5 improved PreS1-MA 18/7 competition. The correlation of MA 18/7 vs. NT50 showed there was a positive correlation observed between live virus neutralization and PreS1 monoclonal antibody competition. The ability of antibodies generated by immunization to induce complement activity (ADCD activity) and phagocytosis activity in mouse monocytes and neutrophils (mADCP activity) was assessed. The results of the ADCD activity assay show that Group 5 antibodies elicit high complement activity to PreS1 and PreS1, PreS2. The results of the mADCP activity assay show that Group 5 antibodies elicit high phagocytosis activity in mouse monocytes and neutrophils to PreS1 and PreS1, PreS2 (FIG.1I). Also, Small SVPs induce high complement and phagocytosis activity. Cell-mediated responses to envelope antigen constructs were measured on Day 43 using Meso Scale Discovery (MSD) Immunoassay to measure the levels of targets within a sample. Briefly, samples were stimulated at 2 µg/mL with overlapping peptide pool for 6 hours (Genotype A). The results show that PreS1 and PreS2 engineered constructs 194 Attorney Docket No.45817-0192WO1 / MTX1067.20 (Groups 3, 5, 7) are immunogenic. UL130sigP_PreS1S2_LuS (Group 5) elicits the highest on-target response. Addition of PreS2 appears to dampen T-cell reactivity to PreS1 when displayed on ferritin. Results also showed that the Small SVP construct (Group 11) is highly immunogenic and outperform commercially available vaccines (Groups 13 and 15). The results of this study demonstrated that mRNA vaccine constructs encoding HBV envelope antigens elicit antibody titers, a correlate of protection for prophylactic HBV vaccine, in mice as compared to two commercially available vaccines, Heplisav B and Remcombivax. Example 2. HBV Polymerase protein Immunogenicity Study A screen was conducted using vaccine compositions comprising lipid nanoparticles encapsulating an mRNA polynucleotides having an ORF encoding an HBV polymerase protein to test the immunogenicity of the vaccines. Antigen designs of immunogens encoded by the mRNA are indicated in Table 6. The antigens in the vaccine compositions administered were variants of the HBV polymerase protein. Compositions in Groups 1 and 2 comprised mRNA polynucleotides having an ORF encoding HBV wild-type polymerase protein from genotype D. Compositions in Groups 3 and 4 comprised mRNA polynucleotides having an ORF encoding the HBV-D polymerase protein with eight amino acid mutations. The eight amino acid mutations were in the TP domain, Spacer domain and RNAseH domain. Specifically, the eight amino acid mutations were substitutions to alanine at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781. Compositions in Groups 5 and 6 comprised mRNA polynucleotides having an ORF encoding the HBV-D polymerase protein with ΔYMDD (SEQ ID NO: 368; “YMDD” is disclosed as SEQ ID NO: 407), a mutation of the conserved YMDD motif (SEQ ID NO: 407) in associated with resistance to antiviral treatment. Group 7 was administered PBS as a control. CB6F1 H-2K^b/d mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum and spleen samples were taken on Day 36. Groups 1, 3, and 5 were administered a dose of 2 μg. Groups 2, 4, and 6 were administered a dose of 0.4 μg. 195 Attorney Docket No.45817-0192WO1 / MTX1067.20 Table 6: HBV polymerase protein construct design Group Composition Format Dose N SEQ # (μg/mouse) ID : e -me a e responses o po ymerase pro e n cons ruc s were measure wee post-boost using spleen samples. Results from the Intracellular Cytokine Staining (ICS) assay indicate that there are highly potent, dose-dependent polyfunctional CD4+ Th-1- biased responses to polymerase protein constructs. Briefly, samples (2⁶ cells/condition) were stimulated with 2 µg/mL overlapping peptide pool (Genotype D). The HBV-D polymerase protein with 8 amino acid mutations elicited the strongest CD4+ T cell responses (Group 3) (FIG.2A). Also, results from the assay stimulation with CD8+ (15- mer) indicate that there were highly potent, polyfunctional T cell responses with cytotoxic potential to polymerase protein constructs (FIG.2B). Example 3. HBV Core protein Immunogenicity Study A screen was conducted using vaccine compositions comprising lipid nanoparticles encapsulating an mRNA polynucleotides having an ORF encoding an HBV core protein to test the immunogenicity of the vaccines. Antigen designs of immunogens encoded by the mRNA are indicated in Table 7. The antigens in the vaccine compositions administered were variants of the HBV core protein. Compositions in Groups 2 and 3 comprised mRNA polynucleotides having an ORF encoding HBV wild-type core protein from genotype D. Compositions in Groups 4 and 5 comprised mRNA polynucleotides having an ORF encoding a truncated HBV-D core protein. The truncated core protein included amino acids 1-149. Compositions in Groups 6 and 7 comprised mRNA polynucleotides having an ORF encoding the truncated 196 Attorney Docket No.45817-0192WO1 / MTX1067.20 HBV-D core protein with an amino acid mutation at position 132. The amino acid mutation at position 132 was a tyrosine to alanine mutation. Group 1 was administered PBS as a control. CB6F1 mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum and spleen samples were taken on Day 36. Groups 2, 4, and 6 were administered a dose of 2 μg. Groups 3, 5, and 7 were administered a dose of 0.4 μg. Table 7: HBV core protein construct design Group Composition Format Characterization Dose N SEQ # (μg/mouse) ID : Cell-mediated responses to mRNA polynucleotides having an ORF encoding core protein constructs were measured week 1 post-boost using spleen samples. Results from the Intracellular Cytokine Staining (ICS) assay indicate that there are highly potent, dose- dependent polyfunctional CD4+ Th-1-biased responses to mRNA polynucleotides having an ORF encoding core protein constructs. (FIG.3A). Briefly, samples (2⁶ cells/condition) were stimulated with 2 µg/mL overlapping peptide pool (Genotype D). Also, results from the assay stimulation with CD8+ (15-mer) indicate that there are highly potent, dose- dependent polyfunctional T-cell responses with cytotoxic potential to mRNA polynucleotides having an ORF encoding core protein constructs (FIG.3B). Example 4. HBV Combination Antigen Immunogenicity Study The following studies were performed to evaluate the immunogenicity of vaccines comprising mRNA polynucleotides having an ORF encoding a combination of HBV 197 Attorney Docket No.45817-0192WO1 / MTX1067.20 envelope (Genotype A), polymerase (Genotype D), and core proteins (Genotype D). Additionally, the functional abilities of antibodies generated by vaccine composition administration was assessed using a neutralization assay. Antigen designs of immunogens encoded by the mRNA are indicated in Tables 8-10. The antigens in the vaccine compositions administered were multivalent mRNA polynucleotides having an ORF encoding HBV envelope, core, and polymerase proteins. Compositions in Group 2 comprised mRNA polynucleotides having an ORF encoding HBV envelope antigen containing the PreS1 and PreS2 domains with a N-terminal signal peptide, and lumazine synthase. Compositions in Group 3 comprised mRNA polynucleotides having an ORF encoding the truncated HBV core protein with amino acids 1-149. Compositions in Group 4 comprised mRNA polynucleotides having an ORF encoding the HBV polymerase protein with eight amino acid mutations. Groups 5-8 were administered a multivalent combination of the constructs in Groups 2-4 at different doses. Group 9 received a multivalent combination of the constructs in Groups 3-4. Group 1 was administered PBS as a control. CB6F1 mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum samples were taken on Day 22 and Day 43. Spleen samples were taken on Day 43. Groups were administered doses according to Tables 8-10. Table 8: HBV combination antigen construct design for FIG.4A UTR SEQ PROTEIN G # C iti _{ID N} ^{D ( )} SE ID 29 29 29 Attorney Docket No.45817-0192WO1 / MTX1067.20 PreS1S2-LuS(A) + Core_149(D) + 89, 65 24, 28, 29 Pol_8mut(D) 3+6+6 Group Composition UTR Dose N Tissue PROTEIN # SEQ (μg) s SEQ ID 9 9 9 9 Attorney Docket No.45817-0192WO1 / MTX1067.20 Table 10: HBV combination antigen construct design for FIGs.4C – 4H Group # Composition Dose (μg) PROTEIN SEQ ID NO 9 9 9 9 Compared to PBS treated mice, Groups 2, 6, 5, 7, and 8 showed enhanced production of HBV PreS1/S2 IgG on Day 22 and Day 43 (FIG.4A). Surprisingly, no antibody interference to PreS1/S2 was observed in combination vaccines. The neutralization activity was measured on Day 43 using the Live Virus Neutralization Assay. A total of 8 mice were pooled per group and each group was run in duplicate. There were no titers observed in PBS (Group 1), Core_149 (D) (Group 3), Pol_8mut (D) (Group 4), or Core_149 (D) + Pol_8mut (D) (Group 9). The UTR-1 (Group 6) achieves approximately 3-fold higher titer than UTR-2 (Group 5). Groups 7 and 8 achieve comparable titers, and both are higher than the group that received the lowest dose, Group 5. Overall, no neutralization defect was observed in combination vaccines (FIG.4B). Cell-mediated responses to envelope antigen constructs were measured using Intracellular Cytokine Staining (ICS). Briefly, samples (2⁶ cells/condition) were stimulated with 2 µg/mL overlapping peptide pool (PreS1S2 Genotype A, Core Genotype D, and Pol Genotype D). The results show that any existing T-cell interference to 200 Attorney Docket No.45817-0192WO1 / MTX1067.20 PreS1/S2 and core in combination vaccines can be minimized by increasing the dose and optimizing conditions such as UTRs. (FIGs.4C-4H). Example 5. HBV Envelope Antigen Durability Study The following studies were performed to evaluate the durability of vaccines comprising mRNA polynucleotides having an ORF encoding a combination of HBV envelope (Genotype A) antigen variants based on immunogenicity over a 6-month length of time. Additionally, the functional abilities of antibodies generated by vaccine composition administration was assessed using a neutralization assay. Antigen designs of immunogens encoded by the mRNA are indicated in Tables 11, 13-16. The antigens in the mRNA vaccine compositions administered were variants of the HBV envelope antigen. Compositions in Group 1 comprised HBV large envelope antigen with a signal peptide and two alanine mutations. Compositions in Groups 2 and 3 comprised mRNA encoding the PreS1 and PreS2 domains with a signal peptide, and lumazine synthase. Compositions mRNA polynucleotides having an ORF encoding in Group 4 comprised the PreS1 and PreS2 domains with a signal peptide, and ferritin. Compositions in Groups 5 and 6 were mRNA polynucleotides having an ORF encoding HBV Small envelope antigen SVP. Compositions in Groups 7-14 comprised mRNA polynucleotides having an ORF encoding HBV large envelope antigen with a N-terminal signal peptide and two alanine mutations presented with Middle and Small envelope antigens at different ratios on SVPs. Group 15 was administered SVP with RECOMBIVAX HB® adjuvated with alum (Merck Alum). Group 16 was administered PBS as a control. CB6F1 mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum samples were taken on Days 22, 43, 56 (1-month post-boost), 87 (2-months post-boost), 143 (4-months post-boost), and 226 (6-months post-boost). Spleen samples were taken on Day 43 (Groups 2, and 5), and Day 226. Groups 1-6 were administered a dose of 1 μg. Groups 7, 9, 11, and 13 were administered a dose of 3 μg. Groups 8, 10, 12, and 14 were administered a dose of 0.3 μg. Group 15 was administered a dose of 0.5 μg. 201 Attorney Docket No.45817-0192WO1 / MTX1067.20 Ratios of HBV envelope antigen are presented in Tables 11, 13-16 as UL130sigP_Large_S_Ag_2Ala : Middle : Small. Table 11: HBV envelope antigen construct design for FIG.5A Group # Composition Dose (μg) Sampling day SEQ ID NO: 1 UL130sigP_Large_S_Ag_2Ala 1 43 18 Table 13: HBV envelope antigen construct design for FIGs.5B, 5C, 5J _{Group # Composition Dose (μg)} ^{SEQ ID NO:} Table 14: HBV envelope antigen construct design for FIG.5D 202 Attorney Docket No.45817-0192WO1 / MTX1067.20 _{Group # Composition Dose (μg)} ^{SEQ ID NO:} 1_{Large_2Ala 1} ¹⁸ _{Group # Composition Dose (μg)} ^{SEQ ID NO:} 1_{PBS N/A} - a e e e ope a ge co s uc es g o s. , , , _{Group # Composition Dose (μg)} ^{SEQ ID NO:} 1_{Large 2Ala 1} ¹⁸ The total HBV-specific IgG levels were measured on Days 22, 43, 57, 87, 143 and 226 for Groups 1, 3, 4, and 16. Compared to PBS treated mice, Groups 1, 3, and 4 showed enhanced production of HBV PreS1/S2 IgG. The PreS1/S2 binding IgG titers persisted 6 months following immunization with membrane anchored and soluble/secreted nanoparticulated antigens. Compared to PBS treated mice, Groups 3 and 4 showed enhanced production of HBV small IgG. The Small binding IgG titers persisted 6 months following immunization with superior responses to soluble/secreted subviral particles. The neutralization activity of test groups 1, 3, 4, 6, and 15 and control group 16 was measured Days 43, 57, 87, 143 using the Live Virus Neutralization Assay. High levels of neutralization titers were observed in test groups. There was no observed loss over time in neutralization titers for Groups 1, 6, and 15. There was approximately a 2- fold drop in titers at Day 143 timepoint for secreted nanoparticles (Groups 3 and 4). 203 Attorney Docket No.45817-0192WO1 / MTX1067.20 Overall, functional antibodies were still detectable at least 4 months following prime boost (FIG.5A). Cell-mediated responses to envelope antigen constructs were measured on Day 226 (6-months post-boost) using Intracellular Cytokine Staining (ICS) or AIM (cytokine- independent). Briefly, samples were stimulated with peptides of either PreS1/S2 peptide pool, or small peptide pool, or large peptide pool. The results show that there was evidence for memory PreS1/S2 directed memory CD4+ and CD8+ T-cell responses 6 months following immunization, with highest response observed following PreS1/S2 LuS immunization (FIGs.5B-5E). Also, there was evidence for memory Large (PreS1/S2/small) directed memory CD4+ and CD8+ T-cell responses 6 months following immunization, with mRNA-LNP encoded membrane anchored large and SVP designs outcompeting alum adjuvanted recombinant SVPs (FIGs.5G-5I). The results also show evidence for small-specific memory CD4+ and CD8+ T-cell responses 6 months following immunization, with mRNA-LNP encoded membrane anchored large and SVP designs outcompeting alum adjuvanted recombinant SVPs (FIGs.5K-5N). Plasma cells directed to small and PreS1/S2 were quantified in spleen and bone marrow samples. The results showed that preS1/preS1S2 - specific ASC were not detected in spleens after 6 month of immunization with Large_2Ala, preS1S2-LuS or preS1S2-Ferritin. Small-specific B cells were detected with small SVP and Recombivax HB in both spleens and bone marrow. The frequency of Small-specific ASC tends to be higher with small SVP immunization in spleens, while comparable in bone marrow with the two groups (FIGs.5O and 5J). The frequencies of preS1/preS1S2 LLPC in bone marrows are comparable between Large_2Ala, preS1S2-LuS and preS1S2-Ferritin immunizations. Example 6. HBV Envelope and Core protein Immunogenicity Study The following studies were performed to evaluate the immunogenicity of mRNA polynucleotides having an ORF encoding a combination of HBV envelope (Genotype A) and HBV core (Genotype D) antigen variants. Additionally, the functional abilities of 204 Attorney Docket No.45817-0192WO1 / MTX1067.20 antibodies generated by vaccine composition administration was assessed using a neutralization assay. Antigen designs of immunogens encoded by the mRNA are indicated in Tables 17 and 18. The antigens in the vaccine compositions administered were combinations of the HBV envelope and core proteins. Compositions in Group 2 comprised mRNA polynucleotides having an ORF encoding a truncated HBV core protein containing amino acids 1-149. Compositions in Groups 3 and 4 comprised mRNA polynucleotides having an ORF encoding the PreS1 and PreS2 domains with a N-terminal signal peptide, and lumazine synthase. Compositions in Groups 5 and 6 comprised mRNA polynucleotides having an ORF encoding the PreS1 and PreS2 domains and wild-type core protein. Compositions in Groups 7 and 8 comprised mRNA polynucleotides having an ORF encoding the PreS1 and PreS2 domains and truncated core protein containing amino acids 1-149. Group 1 was administered PBS as a control. CB6F1 mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum samples were taken on Day 22 and Day 43. Spleen samples were taken on Day 43. Groups 2, 3, 5, and 7 were administered a dose of 2 μg. Groups 4, 6, and 8 were administered a dose of 0.4 μg. Table 17: HBV envelope and core protein construct design for FIG.6A Group Composition Format Dose N Tissues PROTEIN # ( ) SEQ ID NO Attorney Docket No.45817-0192WO1 / MTX1067.20 8 PreS1S2- Secreted 0.4 8 Sera 27 Core_149 nanoparticle Spleens Group # Composition Dose (μg) PROTEIN SEQ ID NO 1 Core 149 2 28 e o a -spec c g e e s e e easu e o ay and 43. It was demonstrated that PreS1/S2-Core149 (Group 7 and 8) elicits comparable PreS1 binding IgG titers to LuS immunogen (Groups 3 and 4). Also, PreS1/S2-Core149 (Groups 7 and 8) elicited comparable core binding IgG titers to LuS immunogen (Group 2). The neutralization activity was measured on Day 43 using the Live Virus Neutralization Assay. Pools were generated and each group was run in duplicate and shown in FIG.6 Neutralizing antibodies were observed in Groups 3-8. The PreS1S2_LuS construct (Group 3) at 2 µg dose achieved highest neutralizing titers. Also, PreS1S2- Core_wt(Group 5) and PreS1S2-Core_149 (Groups 7 and 8) constructs at 2 µg dose achieved high titers as shown in (FIG.6A). The ability of antibodies generated by immunization to induce complement activity (ADCD activity) and phagocytosis activity in mouse monocytes and neutrophils (mADCP activity) was assessed. Each of PreS1/S2-Core149 (Groups 7 and 8) and LuS immunogen (Groups 3 and 4) were demonstrated to elicit Fc effector functionality. Cell-mediated responses to envelope antigen constructs were measured (Day 43. Intracellular Cytokine Staining (ICS). Stimulating 2e6 cells/condition with 2 ug/mL overlapping peptide pool (PreS1S2 Genotype A, Core Genotype D)). Briefly, samples were stimulated with either core peptide pool or PreS1/S2 peptide pools. The results 206 Attorney Docket No.45817-0192WO1 / MTX1067.20 showed that compared to Core149 alone, core-T cell responses were dampened somewhat following PreS1/S2_Core149 immunization, (although still higher than with PReS1/S2 alone) while PreS1/S2 responses were not negatively impacted (FIG.6B-6C). Example 7. Immunogenicity Study of Trimeric mRNA polynucleotides having an ORF encoding antigens from Alternative HBV Genotypes. The following studies were performed to evaluate the immunogenicity of mRNA polynucleotides having an ORF encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes. The HBV Genotypes tested include A, B, C, and D. Additionally, the functional abilities of antibodies generated by vaccine composition administration was assessed using a neutralization assay. Antigen designs of immunogens encoded by the mRNA are indicated in Tables 19 and 20. The antigens in the vaccine compositions administered were combinations of the HBV envelope, core, and polymerase proteins. The envelope antigen tested was the PreS1/S2 domain fused to lumazine synthase. The core protein tested was a truncated HBV core protein containing amino acids 1-149. The polymerase protein tested contained eight mutations relative to the wild-type sequence. Compositions in Groups 2 and 3 received the combination of three HBV antigens from Genotype A. Compositions in Groups 4 and 5 received mRNA polynucleotides having an ORF encoding the combination of three HBV antigens from Genotype B. Compositions in Groups 6 and 7 received mRNA polynucleotides having an ORF encoding the combination of three HBV antigens from Genotype C. Compositions in Groups 8 and 9 received mRNA polynucleotides having an ORF encoding the combination of three HBV antigens from Genotype D. Group 1 was administered PBS as a control. CB6F1 mice were administered a prime dose on Day 1 and a booster dose on Day 29. Serum samples were taken on Day 22 and Day 43. Spleen samples were taken on Day 43. Groups were administered a dose according to Tables 19 and 20. Table 19: HBV combination antigen from alternative Genotype construct design for FIG.7A 207 Attorney Docket No.45817-0192WO1 / MTX1067.20 Grou Composition Genotyp UT Dos N Tissue PROTEI p # e R e s N SEQ , , , , , , , , Attorney Docket No.45817-0192WO1 / MTX1067.20 Table 20: HBV combination antigen from alternative Genotype construct design for FIGs.7B-7D Group # Composition Dose (μg) PROTEIN SEQ ID NO The neutralization activity was measured on Day 43 using the Live Virus Neutralization Assay. Eight mice were pooled per group and each group was run in duplicate. The results show that all test groups elicited high neutralizing titers with Genotype D constructs (Groups 8 and 9) having the highest titers of the genotypes tested against HBV-D. Further, a dose dependent effect was not observed on neutralization titer within a given genotype under test conditions. No appreciable difference in neutralizing capacity to HBV-D was observed across genotypes. There was a slight increase observed in neutralization titer when dose was tripled (FIG.7A). Cell-mediated responses to envelope antigen constructs were measured on day 43 from spleen samples using intracellular cytokine staining. Briefly, samples (2⁶ cells/condition) were stimulated with 2 µg/mL overlapping peptide pool (PreS1S2 Genotype A-D, Core Genotype A-D, and Polymerase A-D). The results from the 209 Attorney Docket No.45817-0192WO1 / MTX1067.20 PreS1/S2 peptide pool showed that in the mRNA polynucleotides having an ORF encoding the combination of three HBV antigens of Genotype A (followed by genotype C) generates highly polyfunctional CD8+ and CD4+ T cells. Further, Genotype B and D displayed minimal CD8+ T cell responses. Therefore, despite higher HBV Genotype D expression for PreS1 by western blot (data not shown), T cell responses to HBV Genotype A were highest, with lower reactivity to HBV Genotype D peptides (FIG.7B). The results from the core peptide pool showed that the combination of three HBV antigens of Genotype D elicited highly polyfunctional CD8+ and CD4+ T cells and that a 6 µg dose displays a boost in T cell cytokines. Finally, HBV Genotype D elicited the highest T cell reactivity to core (FIG.7C). The results from the polymerase peptide pool show that the combination of three HBV antigens of Genotype B and D elicit highly polyfunctional CD8+ and CD4+ T cells and that a 6 µg dose leads to a boost in T cell cytokines. Finally, the HBV Genotypes B and D elicit the greatest T cell reactivity to Polymerase (FIG.7D). Example 8. Robust CTL-specific killing in response to Trivalent mRNA vaccine administration. Mice were primed and boosted on D1/21 with 3+6+6 µg of PreS1S2_LuS + Core_149 + Pol_8mut. On Day 29, naïve mouse splenocytes were peptide pulsed for 1 hour with 10 µg/mL of preidentified immunogenic epitopes and labeled with CD45.2 for FACS identification post-adoptive transfer. Peptide-pulsed APCs were also labeled with varying amounts of Cell Trace Violet (CTV) or Cell Trace Far Red (CTFR) to distinguish the specific populations. Peptide-pulsed cells (200 µl) were intravenously adoptively transferred (AT) into vaccinated mice on D29. Spleens from vaccinated mouse were collected 16 hours later (D30) and single cell suspensions were measured via flow cytometry to determine the degree of killing calculated as [1- (DMSO group/Peptide- pulsed group Naïve)/(DMSO group/Peptide-Pulsed group Experimental)]x100%. The results are shown in FIG 8. The figure is a bar graph depicting the effect of administration of the trivalent mRNA vaccine encoding a combination of HBV envelope, 210 Attorney Docket No.45817-0192WO1 / MTX1067.20 core, and polymerase proteins from different HBV Genotypes and measuring CTL- specific killing. CTL-specific killing assessed in peptide pulsed cells was robust for each antigen (PreS1, Core, and Polymerase). All groups tested exhibited over 85% killing of peptide-pulsed cells. Example 9. Demonstration of Immunogenicity resulting from Quadrivalent mRNA vaccine administration. A study involving mice administered a quadrivalent mRNA vaccine encoding a combination of HBV envelope, small, core, and polymerase proteins from different HBV Genotypes was conducted. The Groups are shown in the following Tables 21 and 22. Table 21: HBV combination antigen from alternative Genotype construct design for FIGs.9B-9C G_{roup # Composition Dose (μg)} ^{SEQ ID NO:} ⁹ ⁹ Table 22: HBV combination antigen from alternative Genotype construct design for FIG.9D Group Co SEQ ID NO: # mposition Dose (μg) 9 ⁹ 211 Attorney Docket No.45817-0192WO1 / MTX1067.20 The data demonstrate that antigens are immunogenic in quadrivalent combination (FIG.9). FIG.9A shows that a quadrivalent vaccine induced comparable anti-PreS1/S2 IgG titer and lower anti-Small IgG compared to the respective monovalent vaccine. FIG. 9B shows that a quadrivalent vaccine induced lower live virus neutralization as compared to Small monovalent vaccine, but higher neutralization compared to PreS1S2_LuS vaccine alone. FIG.9C shows that antibody induced by quadrivalent vaccine displayed enhanced antibody-dependent cellular cytotoxicity (ADCC) as compared to PreS1S2 monovalent vaccine. FIGs.9D show that a quadrivalent vaccine elicited robust, yet slightly decreased, CD8+ and CD4+ (Th1-dominated) T cells to all four antigens as compared to monovalent vaccines. Example 10. Combination siRNA/ASO and mRNA LNP therapy The following studies are performed to evaluate a combination with direct-acting modalities to achieve long-term viral suppression and functional cure. The goal of this combination therapy is to improve rates of functional cure upon nucleos(t)ide analog (NUC) therapy discontinuation (HBV DNA <LLOQ, ALT<3x ULN, HBeAg-, HBsAg <10 IU/mL at ~6 months post-treatment). Subjects are administered NUC therapy. After administration of NUC therapy baseline levels of HBsAg change (Log10 IU/mL) is measured. Next, siRNA or ASO treatment (before or concomitant to vaccine) is administered. Subjects are administered three doses of siRNA or ASO treatment. After siRNA treatment subjects are administered three to five doses of mRNA LNP vaccine encoding HBV antigen. Blood samples are collected from subjects before siRNA or ASO treatment, after siRNA or ASO treatment and before mRNA LNP vaccine, after LNP vaccine and six months after treatment. The subjects that receive siRNA or ASO treatment and mRNA LNP vaccine will not show a viral rebound after NUC treatment is terminated. Example 11. Phase 1/2 study 212 Attorney Docket No.45817-0192WO1 / MTX1067.20 The following Phase 1/2 study is performed to in two parts, Part A and Part B to evaluate mRNA LNP vaccine encoding HBV antigen. Part A includes safety and reactogenicity data and informs selection of highest dose for Part B where CHB with higher sAg levels are enrolled. Part B includes safety and immunogenicity/viral endpoints and informs decision for partnership with siRNA for Phase 2. Subjects are 66 adults, ages 18-70 years old with chronic HBV infection. The Part A Population is CHB with moderate sAg (100-3,000 IU/ml) (N=30), NUC-treated, negative eAg and HBV DNA. Part A is a randomized, dose-ranging study. Dose are given at 0, 2 Month and 4 Month with a 6 Month safety follow. Dose escalation as FIH, using higher dose levels. IA-1: 1M PD2 safety data (focused on decompensated hepatitis) to inform highest dose for Part B to expand into broader CHB cohorts (higher sAg and eAg+). The endpoints are safety and reactogenicity. The exploratory immune endpoints include CMI, change sAb GMT. Three doses are tested, 50 μg, 100 μg, and 150 μg. The dose for Part B is selected as the highest dose based on safety data. The Part B Population expands CHB to higher range of sAg, including <5,000 IU/ml ±eAg (N=36). Part B is a randomized, placebo-controlled study. Doses are given at 0 Month, 2 Month, 4 Month, ± 2 additional doses (based on GLP tox/ 6 Month safety follow-up). IST: Lead-in PD1 safety data from lower sAg cohort. IA-2: Safety and immune data 1M PD3 (of Part B) for decision to proceed with P201 in combinations with siRNA. The endpoints include safety of selected dose across wide CHB sAg levels and the panel of viral (sAg loss, sAb, crAg, HBV RNA/DNA) and immune (HBV-specific CMI, sAb GMT) endpoints. Example 12. Phase 1/2 study The following Phase 1/2 study is performed in two parts, Part A and Part B to evaluate mRNA LNP vaccine encoding HBV antigen. Part A includes safety and reactogenicity data and informs selection of highest dose for Part B where CHB with higher sAg levels are enrolled. Part B includes safety and immunogenicity/viral endpoints 213 Attorney Docket No.45817-0192WO1 / MTX1067.20 and informs go/no-go decision for partnership with siRNA for P201 Phase 2. Subjects are 66 adults, ages 18-70 years old with chronic HBV infection. In Part A screening is performed 28 days before the first dose is administered (-28 days). Vaccine doses are administered Day 1 (D1), Month 1, and Month 3. Safety labs are collected -28 days, D1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 9, and Month 12. Viral/immune endpoints are collected D1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 9, and Month 12. In Part B screening is performed 28 days before the first dose is administered (-28 days). Vaccine doses are administered Day 1 (D1), Month 1, and Month 3. Additional vaccines doses are administered in Month 6 and Month 9, if needed. Safety labs are collected -28 days, D1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 9, and Month 15. Viral/immune endpoints are collected D1, Month 1, Month 2, Month 3, Month 4, Month 6, Month 9, and Month 15. Example 13. Phase 2 combination study The following Phase 2 study is performed to evaluate mRNA LNP vaccine encoding an HBV antigen in combination with an siRNA in adults, ages 18-70 years old, with chronic HBV infection. Study subjects have chronic HBV with range of sAg (low <10,000 and high>10,000 sAg, eAg-negative). This is a randomized, placebo-controlled. There is a 6-12 month follow up after treatment course. Multiple combinations may be tested. For instance, variables such as increasing mRNA dosing by five times and changing intervals may be modified. Also, multiple siRNA dose and dosing schedules may be tested. Also, addition of immune modulators (PD-1, TLR7, Peg-IFN) may be tested. Based on the IA data a determination of whether to undertake NUC-withdrawal may be made. The endpoints are safety and tolerability of combinations, sAg decline, sAb seroconversion rate, immune endpoint with panel of endpoints (sAg/Ab, crAg, HBV RNA, CMI). 214 Attorney Docket No.45817-0192WO1 / MTX1067.20 Example 14. Immunogenicity and HBV cross-genotype reactivity of trivalent mRNA HBV vaccine in non-human primates The objective of this study was to assess the immunogenicity and HBV cross- genotype reactivity of humoral and cellular immune responses to HBV antigens in non- human primates following immunization with a trivalent mRNA vaccine encoding a combination of HBV envelope, core, and polymerase proteins. The trivalent mRNA vaccine used in this study was composed of three mRNAs encoding for (i) the PreS1- PreS2 domains of HBsAg (HBV genotype A sequence) fused to a lumazine synthase monomer (PreS1S2_LuS; protein of SEQ ID NO:24, encoded by mRNA of SEQ ID NO:99 and corresponding construct sequence of SEQ ID NO:412), (ii) the HBV Core (HBV genotype D sequence) truncated in position 149 (Core_149: protein of SEQ ID NO:28, encoded by mRNA of SEQ ID NO:103 and corresponding construct sequence of SEQ ID NO:413), and (iii) the HBV Polymerase (HBV genotype D sequence) inactive mutant (Pol_8mut; protein of SEQ ID NO:29, encoded by mRNA of SEQ ID NO:108 and corresponding construct sequence of SEQ ID NO:414). The three mRNAs were encapsulated at a mass ratio of 20:40:40%, respectively, in lipid nanoparticles (LNPs) containing four mixed lipids: Compound (I-25) (ionizable lipid); PEG2000-DMG; 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC); and cholesterol. The study group contained six male Cambodian-origin Cynomolgus macaques approximately 2-6 years of age. On Day 0, all animals received a priming dose of 150 ug of the trivalent mRNA vaccine via intramuscular injection in a volume of 500 ul. Repeat doses were administered on Days 28 and 56. Blood samples for serum and peripheral blood mononuclear cell (PBMC) isolation were collected on Days 0, 14, 42, and 70, and splenocyte samples were collected from all animals on Day 70. Immunization with the trivalent mRNA vaccine elicited serum IgG targeting the vaccine-encoded PreS1S2 (genotype A) antigen on Day 14 (2 weeks post prime), Day 42 (2 weeks post 1st boost), and Day 70 (2 weeks post 2nd boost) (FIG.10). In addition, serum antibodies induced by the vaccination exhibited cross-reactive binding to the PreS1S2 antigens of HBV genotypes B, C, and D on Day 14 (2 weeks post prime), Day 215 Attorney Docket No.45817-0192WO1 / MTX1067.20 42 (2 weeks post 1st boost), and Day 70 (2 weeks post 2nd boost) (FIG.10). Serum from Cynomolgus macaques immunized with the trivalent mRNA vaccine exhibited HBV neutralization on Day 42 (2 weeks post 1st boost) and Day 70 (2 weeks post 2nd boost) (FIG.11). T cell responses specific for vaccine-encoded HBV PreS1S2 (genotype A), HBV Core (genotype D), and HBV Polymerase (genotype D) were elicited in immunized Cynomolgus macaques on Days 14 (2 weeks post prime), Day 42 (2 weeks post 1st boost), and Day 70 (2 weeks post 2nd boost). In splenocytes collected on Day 70, CD8+ T cell responses elicited by the trivalent mRNA vaccine were characterized by upregulation of cytotoxicity markers (CD107a, IFN-γ, TNF-α, IL-2) (FIG.12, top panel) and CD4+ T cell responses were characterized by a Th1 signature (IFN-γ, TNF-α, IL-2) (FIG.12, bottom panel). In splenocytes collected on Day 70, CD8+ and CD4+ T cell responses elicited by the trivalent mRNA vaccine demonstrated cross-reactivity to the PreS1S2 antigen of HBV genotypes B, C, and D, as well as the Core and Polymerase antigens of HBV genotypes A, B, and C (2 weeks post 2nd boost) (FIG.12). These findings demonstrate that the trivalent mRNA vaccine effectively induces a cross-reactive immune response against HBV genotypes A, B, C, and D. The ability to induce a cross-reactive immune response allows the vaccine to be used in the treatment or prevention of HBV infection of diverse genotypic origin, while reducing or avoiding the need to include in the vaccine mRNAs encoding proteins derived from many genotypes. Example 15. Therapeutic efficacy of trivalent mRNA HBV vaccine in a surrogate chronic HBV infection mouse model The objective of this study was to assess in adeno-associated virus-hepatitis B virus (AAV-HBV) infected mice the in vivo efficacy of treatment with a trivalent mRNA vaccine encoding a combination of HBV envelope, core, and polymerase proteins. The trivalent mRNA vaccine used in this study was composed of three mRNAs encoding for (i) the PreS1-PreS2 domains of HBsAg (HBV genotype A sequence) fused to a lumazine synthase monomer (PreS1S2_LuS; protein of SEQ ID NO:24, encoded by mRNA of 216 Attorney Docket No.45817-0192WO1 / MTX1067.20 SEQ ID NO:99 and corresponding construct sequence of SEQ ID NO:412), (ii) the HBV Core (HBV genotype D sequence) truncated in position 149 (Core_149: protein of SEQ ID NO:28, encoded by mRNA of SEQ ID NO:103 and corresponding construct sequence of SEQ ID NO:413), and (iii) the HBV Polymerase (HBV genotype D sequence) inactive mutant (Pol_8mut; protein of SEQ ID NO:29, encoded by mRNA of SEQ ID NO:108 and corresponding construct sequence of SEQ ID NO:414). The three mRNAs were encapsulated at a mass ratio of 20:40:40%, respectively, in LNPs containing four mixed lipids: Compound (I-25) (ionizable lipid); PEG2000-DMG; 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC); and cholesterol. Male C57BL/6J mice (5-6 weeks old) were employed in this study. After a one- week acclimation period, on Day -30 the mice were injected through the tail vein with vector genomes of recombinant AAV-HBV (rAAV8-1.3HBV, genotype D) according to the following four groupings, based on the amount of viral genome (vg) administered: Group 1: 1×10^10 vg Group 2: 5×10^9 vg Group 3: 1×10^9 vg Group 4: 5×10^8 vg The model verification was conducted 25 days post AAV-HBV injection (Day - 5). On Day 0, mice from the four groups were selected for one of the following treatments: HBV Tx: intramuscular injection of the trivalent mRNA vaccine (3μg of PreS1S2_LuS mRNA + 6 μg of Core_149 mRNA + 6 μg of Pol_8mut mRNA); 4 doses PBS (control): intramuscular injection of PBS; 4 doses The mice were given treatments on Day 0, Day 14, Day 28, and Day 42 and then euthanized on Day 63. Serum samples from the mice were collected on Day -30, Day -5, Day 14, Day 28, Day 42, and Day 63 for serum HBsAg and serum HBeAg level measurement. 217 Attorney Docket No.45817-0192WO1 / MTX1067.20 Serum HBsAg levels and HBeAg levels of PBS treated (control) mice corresponded to the amount of viral genome administered, with Group 1 having the highest levels, followed in descending order by Groups 2, 3, and 4 (FIGS.13A-13B). For Groups 3 and 4, HBV Tx treatment reduced levels of both HBsAg and HBeAg (FIGS.13A-13B). For Group 3 (1 × 10^9 vg) and Group 4 (5 × 10^8 vg), on Day 14, Day 28, Day 42, and Day 63, the serum HBsAg levels of HBV Tx-treated mice were statistically significantly lower than those of PBS-treated mice (FIG.13A). For Group 3 (1 × 10^9 vg), the serum HBsAg levels of HBV Tx-treated mice decreased gradually, with serum HBsAg levels of HBV Tx-treated mice below the detection limit on Day 28, Day 42, and Day 63 (FIG.13A). For Group 4 (5 × 10^8 vg), the serum HBsAg levels of HBV Tx- treated mice were below the detection limit on Day 14, Day 28, Day 42, and Day 63 (FIG.13A). The serum HBsAg levels of PBS-treated mice remained at a constant level during the study (FIG.13A). For Group 3 (1 × 10^9 vg), on Day 28, Day 42, and Day 63, the serum HBeAg levels of HBV Tx-treated mice were statistically significantly lower than those of PBS- treated mice (FIG.13B). For Group 4 (5 × 10^8 vg), on Day 14, Day 28, Day 42, and Day 63, the serum HBeAg levels of HBV Tx-treated mice were statistically significantly lower than those of PBS-treated mice (FIG.13B). For Group 3 (1 × 10^9 vg), the serum HBeAg levels of HBV Tx-treated mice decreased gradually, with serum HBeAg levels of HBV Tx-treated mice below the detection limit on Day 42 and Day 63 (FIG.13B). For Group 4 (5 × 10^8 vg), the serum HBeAg levels of HBV Tx-treated mice were below the detection limit on Day 28, Day 42, and Day 63 (FIG.13B). The serum HBeAg levels of PBS-treated mice remained at a constant level during the study (FIG.13B). Mice that received four HBV Tx treatments or four PBS treatments were assessed for expression of the HBV core antigen in the liver (the target organ of HBV infection) at the conclusion of the study. The left lateral, medial, and right lateral lobes of all mice were collected on Day 63 for immunohistochemistry staining of the HBV core antigen. Consistent with the observed serum HBV biomarker changes, administration of the 218 Attorney Docket No.45817-0192WO1 / MTX1067.20 trivalent mRNA vaccine induced clearance of the HBV core antigen signal in livers of mice with low viral load, indicating the elimination of HBV-positive hepatocytes (FIG. 14). These findings demonstrate that the trivalent mRNA vaccine is effective at inducing clearance of HBV biomarkers in mice with low viremia. Example 16. Therapeutic efficacy of trivalent mRNA HBV vaccine in combination with immunomodulatory antibodies in a surrogate chronic HBV infection mouse model The objective of this study was to assess the in vivo efficacy of treatment with a trivalent mRNA vaccine in combination with immunomodulatory antibodies in AAV- HBV infected mice. The trivalent mRNA vaccine used in this study was composed of three mRNAs encoding for (i) the PreS1-PreS2 domains of HBsAg (HBV genotype A sequence) fused to a lumazine synthase monomer (PreS1S2_LuS; protein of SEQ ID NO:24, encoded by mRNA of SEQ ID NO:99 and corresponding construct sequence of SEQ ID NO:412), (ii) the HBV Core (HBV genotype D sequence) truncated in position 149 (Core_149: protein of SEQ ID NO:28, encoded by mRNA of SEQ ID NO:103 and corresponding construct sequence of SEQ ID NO:413), and (iii) the HBV Polymerase (HBV genotype D sequence) inactive mutant (Pol_8mut; protein of SEQ ID NO:29, encoded by mRNA of SEQ ID NO:108 and corresponding construct sequence of SEQ ID NO:414). The three mRNAs were encapsulated at a mass ratio of 20:40:40%, respectively, in LNPs containing four mixed lipids: Compound (I-25) (ionizable lipid); PEG2000-DMG; 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); and cholesterol. Male C57BL/6J mice (5-6 weeks old) were employed in this study. After a one- week acclimation period, on Day -30 the mice were injected through the tail vein with vector genomes of recombinant AAV-HBV (rAAV8-1.3HBV, genotype D) according to the following four groupings, based on the amount of viral genome (vg) administered: Group 1: 1×10^10 vg Group 2: 5×10^9 vg 219 Attorney Docket No.45817-0192WO1 / MTX1067.20 Group 3: 1×10^9 vg Group 4: 5×10^8 vg The model verification was conducted 25 days post AAV-HBV injection (Day - 5). On Day 0, mice from the four groups were selected for one of the following treatments: HBV Tx: intramuscular injection of the trivalent mRNA vaccine (3μg of PreS1S2_LuS mRNA + 6 μg of Core_149 mRNA + 6 μg of Pol_8mut mRNA); mice were given HBV Tx treatments on Day 0, Day 14, Day 28, and Day 42 and then euthanized on Day 63. HBV Tx + aOX40/PD-L1: HBV Tx as above, followed by intraperitoneal injection of 150 µg agonistic anti-OX40 antibody (Bio X Cell, Lebanon, NH; InVivoPlus anti-mouse OX40 (CD134); clone OX-86; catalog number BP0031) and 250 µg antagonistic anti-PD-L1 antibody (Bio X Cell, Lebanon, NH; InVivoMab anti-mouse PD-L1 (B7-H1); clone 10F.9G2; catalog number BE0101); mice were given HBV Tx treatments on Day 0, Day 14, Day 28, and Day 42, aOX40/PD-L1 treatments on Day 49, Day 52, Day 55, Day 58, and Day 61, and then euthanized on Day 63. PBS (control): intramuscular injection of PBS; mice were given PBS treatments on Day 0, Day 14, Day 28, and Day 42 and then euthanized on Day 63. Serum samples from the mice were collected on Day -5, Day 14, Day 28, Day 42, and Day 63 for serum HBsAg, serum HBeAg, and serum HBV DNA level measurement. Consistent with the results of Example 15, treatment with the trivalent mRNA vaccine alone led to only partial and transient reductions in serum HBsAg in Groups 1 and 2, the two highest levels of baseline viremia evaluated, with a subset of treated animals showing modest decreases that rebounded following treatment cessation (FIG. 15). Moreover, quantification of HBV core-positive hepatocytes (indicative of HBV genome persistence) revealed that trivalent mRNA vaccine monotherapy resulted in no significant reduction in Groups 1 and 2 (FIG.16). Administration of an immunomodulatory antibody cocktail of agonistic anti-OX40 and antagonistic anti-PD- L1 antibodies following completion of the HBV Tx treatment regimen resulted in more 220 Attorney Docket No.45817-0192WO1 / MTX1067.20 robust responses for Groups 1 and 2 (FIG.15). This combinatorial regimen led to an approximate 1-log reduction in serum HBsAg (FIG.15) and a ~60% decrease in HBV core-positive hepatocytes in the liver (FIG.16). These findings demonstrate that combining the trivalent mRNA vaccine with immune-stimulatory co-modalities can enhance therapeutic efficacy. ADDITIONAL EMBODIMENTS All of the features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features. From the above description, one skilled in the art can easily ascertain the essential characteristics of the present disclosure, and without departing from the spirit and scope thereof, can make various changes and modifications of the disclosure to adapt it to various usages and conditions. Thus, other embodiments are also within the claims. For example, the Additional Embodiments below are expressly contemplated: Additional Embodiments 1. A composition, comprising a lipid nanoparticle and one or more messenger ribonucleic acid (mRNA), wherein the mRNA comprises: a first open reading frame (ORF) comprising a nucleic acid sequence encoding a hepatitis B virus (HBV) envelope antigen; a second ORF comprising a nucleic acid sequence encoding an HBV core protein; a third ORF comprising a nucleic acid sequence encoding an HBV polymerase protein; and wherein the lipid nanoparticle comprises an ionizable lipid, a neutral lipid, a sterol, and a PEG-modified lipid. 221 Attorney Docket No.45817-0192WO1 / MTX1067.20 2. The composition of embodiment 1, wherein the composition comprises three different mRNAs, and wherein the first ORF is present in a first mRNA, the second ORF is present in a second mRNA, and the third ORF is present on a third mRNA. 3. The composition of any one of embodiments 1-2, wherein the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. 4. The composition of any one of the preceding embodiments, wherein the HBV envelope antigen comprises the amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. 5. The composition of any one of the preceding embodiments, wherein the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 30-42. 6. The composition of any one of the preceding embodiments, wherein the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos: 30-42. 7. The composition of any one of the preceding embodiments, wherein the HBV envelope antigen comprises a PreS1 domain and a PreS2 domain. 8. The composition of any one of the preceding embodiments, wherein the first ORF further comprises a nucleic acid sequence encoding a signal peptide. 222 Attorney Docket No.45817-0192WO1 / MTX1067.20 9. The composition of any one of embodiments 1-4, wherein first ORF further comprises a nucleic acid sequence encoding a lumazine synthase domain. 10. The composition of any one of the preceding embodiments, wherein the HBV core protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. 11. The composition of any one of the preceding embodiments, wherein the HBV core protein comprises the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. 12. The composition of any one of the preceding embodiments, wherein the HBV core protein comprises SEQ ID NOs: 2, SEQ ID NO: 28 or a protein that differs from SEQ ID NOs: 2 or 28 by 1-10 amino acids. 13. The composition of embodiment 12 wherein the HBV core protein is SEQ ID NOs: 26 or 28. 14. The composition of any one of the preceding embodiments, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 43, 44 or 46. 15. The composition of embodiment 14, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos:43, 44 or 46 16. The composition of any one of the preceding embodiments, wherein the HBV polymerase protein comprises an amino acid sequence comprising at least 80%, at least 223 Attorney Docket No.45817-0192WO1 / MTX1067.20 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1 or 29. 17. The composition of embodiment 16, wherein the HBV polymerase protein is a protein that differs from SEQ ID NOs: 1 or 29 by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids. 18. The composition of embodiment 13, wherein the different amino acids are present in a terminal protein domain, a spacer domain, a reverse transcriptase domain, and/or a RNase H domain of the HBV polymerase protein. 19. The composition of any one of the preceding embodiments, wherein the HBV polymerase protein is SEQ ID NOs: 1 or 29. 20. The composition of any one of the preceding embodiments, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 47 or 48. 21. The composition of embodiment 20, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos:47 or 48. 22. The composition of any one of the preceding embodiments, wherein the mRNA comprises a chemical modification. 23. The composition of any of the preceding embodiments wherein the lipid nanoparticle comprises 40-55 mol% of the ionizable lipid, 30-45 mol% of the sterol, 5-15 mol% of the neutral lipid, and 1-5 mol% of the PEG-modified lipid. 224 Attorney Docket No.45817-0192WO1 / MTX1067.20 24. The composition of any one of the preceding embodiments, wherein the ionizable lipid is a lipid of Formula (I): , R₁ is of C_5-30 alkyl, C_5-20 alkenyl, and -R”M’R’; R₂ and R₃ are independently selected from the group consisting of C_1-14 alkyl and C_2-14 alkenyl; R₄ is -(CH₂)_nQ, wherein Q is -OR, and n is selected from 1, 2, 3, 4, and 5; each R₅ is H; each R6 is H; M and M’ are independently selected from -C(O)O- and -OC(O)-; R₇ is H; R is H; R’ is selected from the group consisting of C1-18 alkyl and C2-18 alkenyl; R” is selected from the group consisting of C_3-14 alkyl and C_3-14 alkenyl; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13. 25. A method of treating HBV disease in a subject in need thereof, the method comprising administering to the subject one or more doses of the composition of any one of the preceding embodiments in an effective amount to produce an immune response to an HBV. 26. The method of embodiment 25, comprising administering a single dose of the vaccine to the subject or administering a prime dose and at least one booster dose of the vaccine to the subject. 225 Attorney Docket No.45817-0192WO1 / MTX1067.20 27. A method of treating chronic HBV disease in a subject in need thereof, the method comprising administering to the subject one or more doses of a composition comprising lipid nanoparticle and one or more messenger ribonucleic acid (mRNA), wherein the mRNA comprises at least a first open reading frame (ORF) comprising a nucleic acid sequence encoding a hepatitis B virus (HBV) envelope antigen in an effective amount to produce a cell mediated immune response to the HBV envelope antigen. 28. The method of embodiment 27, wherein the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. 29. The method of embodiment 27 or 28, comprising a second ORF comprising a nucleic acid sequence encoding an HBV core protein. 30. The method of any one of embodiments 27-29, comprising a third ORF comprising a nucleic acid sequence encoding an HBV polymerase protein; and 31. The method of embodiment 30, wherein the composition comprises three different mRNAs, and wherein the first ORF is present in a first mRNA, the second ORF is present in a second mRNA, and the third ORF is present on a third mRNA. 32. The method of any one of embodiments 27-31, wherein the cell mediated immunity is an increase in CD4+ cell activity against HBV. 33. The method of any one of embodiments 27-31, wherein the cell mediated immunity is an increase in CD8+ cell activity against HBV. 226 Attorney Docket No.45817-0192WO1 / MTX1067.20 34. The method of any one of embodiments 27-31, wherein the composition induces functional immunity. 35. The method of any one of embodiments 27-31, wherein the composition induces B cell functional immunity. 36. The method of any one of embodiments 27-35, further comprising administering PEG-IFN monotherapy and/or nucleos(t)ide analogues (NUCs) to the subject. 37. A composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a protein comprising an amino acid sequence that is SEQ ID NOs: 1-7, or 16-29. 227

Claims

Attorney Docket No.45817-0192WO1 / MTX1067.20 What is claimed is: CLAIMS 1. A composition comprising a lipid nanoparticle and one or more messenger ribonucleic acids (mRNAs), wherein the one or more mRNAs comprise: a first open reading frame (ORF) comprising a nucleic acid sequence encoding a hepatitis B virus (HBV) envelope protein; a second ORF comprising a nucleic acid sequence encoding an HBV core protein; and a third ORF comprising a nucleic acid sequence encoding an HBV polymerase protein. 2. The composition of claim 1, wherein the HBV envelope protein comprises a PreS1 domain and a PreS2 domain. 3. The composition of claim 2, wherein the PreS1 domain and a PreS2 domain further comprise a lumazine synthase domain. 4. The composition of any one of claims 1-3, wherein the HBV core protein comprises a Core_149 protein. 5. The composition of any one of claims 1-4, wherein the HBV polymerase protein comprises a Polymerase8mut. 6. The composition of any one of claims 1-5, further comprising a fourth ORF comprising a nucleic acid sequence encoding a Small domain of HBV Envelope protein. 228 Attorney Docket No.45817-0192WO1 / MTX1067.20 7. The composition of any one of claims 1-5, wherein the composition comprises three different mRNAs, and wherein the first ORF is present in a first mRNA, the second ORF is present in a second mRNA, and the third ORF is present in a third mRNA. 8. The composition of any one of claims 1-7, wherein the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. 9. The composition of any one of the preceding claims, wherein the HBV envelope antigen comprises the amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. 10. The composition of any one of the preceding claims, wherein the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 30-42. 11. The composition of any one of the preceding claims, wherein the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos: 30-42. 12. The composition of any one of the preceding claims, wherein the first ORF further comprises a nucleic acid sequence encoding a signal peptide. 13. The composition of any one of the preceding claims, wherein the HBV core protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. 229 Attorney Docket No.45817-0192WO1 / MTX1067.20 14. The composition of any one of the preceding claims, wherein the HBV core protein comprises the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. 15. The composition of any one of the preceding claims, wherein the HBV core protein comprises SEQ ID NO:2, SEQ ID NO:28, or a protein that differs from SEQ ID NO:2 or SEQ ID NO:28 by 1-10 amino acids. 16. The composition of claim 15 wherein the HBV core protein is SEQ ID NO:2 or SEQ ID NO:28. 17. The composition of any one of the preceding claims, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 43, 44 or 46. 18. The composition of claim 17, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos:43, 44 or 46 19. The composition of any one of the preceding claims, wherein the HBV polymerase protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:29. 20. The composition of claim 19, wherein the HBV polymerase protein is a protein that differs from SEQ ID NO:1 or SEQ ID NO:29 by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids. 230 Attorney Docket No.45817-0192WO1 / MTX1067.20 21. The composition of claim 20, wherein the different amino acids are present in a terminal protein domain, a spacer domain, a reverse transcriptase domain, and/or a RNase H domain of the HBV polymerase protein. 22. The composition of any one of the preceding claims, wherein the HBV polymerase protein is SEQ ID NO:1 or SEQ ID NO:29. 23. The composition of any one of the preceding claims, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of SEQ ID NO:47 or SEQ ID NO:48. 24. The composition of claim 23, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of SEQ ID NO:47 or SEQ ID NO:48. 25. The composition of claim 1, wherein the composition comprises: a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:24; a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:28; and a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:29. 26. The composition of claim 1, wherein the composition comprises: 231 Attorney Docket No.45817-0192WO1 / MTX1067.20 a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24; a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:28; and a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:29. 27. The composition of claim 1, wherein the composition comprises: a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24; a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28; and a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29. 28. The composition of any one of the preceding claims, wherein the mRNA comprises a chemical modification. 29. The composition of any of the preceding claims, wherein the lipid nanoparticle comprises an ionizable lipid, a neutral lipid, a sterol, and a PEG-modified lipid. 30. The composition of claim 29, wherein the lipid nanoparticle comprises 40-55 mol% of the ionizable lipid, 30-45 mol% of the sterol, 5-15 mol% of the neutral lipid, and 1-5 mol% of the PEG-modified lipid. 232 Attorney Docket No.45817-0192WO1 / MTX1067.20 31. The composition of claim 29 or 30, wherein the ionizable lipid is a lipid of Formula (IL*): or a salt thereof, wherein: 1^N R is -OH, -NR -C_4-10 with one or more oxo or -N(R^N’R^N’’); R^N is H or C_1-6 alkyl; R^N’ is H or C_1-6 alkyl; R^N’’ is H or C1-6 alkyl; o is 1, 2, 3, or 4; n is 4, 5, 6, 7, or 8; m is 4, 5, 6, 7, or 8; M is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R²; M’ is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R³; or –(C1-6 alkylene)-(C3-8 cycloalkyl)-C1-6 alkyl; R^2b is -H or C_1-10 alkyl; R^2c is C1-8 alkyl or C2-8 alkenyl; ; R^3b is H or C1-8 alkyl; and R^3c is C1-10 alkyl or C2-8 alkenyl. 233 Attorney Docket No.45817-0192WO1 / MTX1067.20 32. The composition of claim 29 or 30, wherein the ionizable lipid is Compound (I- 25) . 33. or the ionizable lipid is Compound (I-25) ; 3-phosphocholine (DSPC); the sterol is cholesterol; and the PEG-modified lipid is PEG2000-DMG. 34. A method of treating HBV disease in a human subject in need thereof, the method comprising administering to the human subject one or more doses of the composition of any one of the preceding claims in an effective amount to produce an immune response to an HBV. 35. The method of claim 34, wherein the HBV disease is chronic HBV disease. 36. The method of claim 34 or 35, comprising administering a single dose of the composition to the human subject. 37. The method of claim 34 or 35, comprising administering at least one prime dose and at least one booster dose of the composition to the human subject. 234 Attorney Docket No.45817-0192WO1 / MTX1067.20 38. The method of claim 34 or 35, comprising administering at least two prime doses and at least two booster doses of the composition to the human subject. 39. The method of claim 34 or 35, comprising administering at least three prime doses and at least two booster doses of the composition to the human subject. 40. The method of claim 34 or 35, comprising administering three prime doses and two booster doses of the composition to the human subject. 41. The method of any one of claims 34-40, wherein the treatment produces sustained undetectable HBsAg and HBV DNA in the human subject. 42. The method of any one of claims 34-40, wherein the treatment produces HBsAg seroconversion in the human subject. 43. The method of any one of claims 34-40, wherein the treatment produces a functional cure in the human subject. 44. The method of any one of claims 34-43, wherein the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD4+ cell activity against HBV. 45. The method of any one of claims 34-44, wherein the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD8+ cell activity against HBV. 46. The method of any one of claims 34-45, further comprising administering PEG- IFN monotherapy and/or nucleos(t)ide analogues (NUCs) to the human subject prior to initiation of treatment with the composition. 235 Attorney Docket No.45817-0192WO1 / MTX1067.20 47. The method of claim 46, wherein the PEG-IFN monotherapy and/or the NUCs are administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. 48. The method of any one of claims 34-47, further comprising administering an siRNA that targets HBV to the human subject prior to initiation of treatment with the composition. 49. The method of claim 48, wherein the siRNA that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. 50. The method of any one of claims 34-49, further comprising administering an antisense oligonucleotide that targets HBV to the human subject prior to initiation of treatment with the composition. 51. The method of claim 50, wherein the antisense oligonucleotide that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. 52. The method of any one of claims 34-51, further comprising administering to the human subject at least one immunostimulatory antibody or at least one mRNA encoding at least one immunostimulatory antibody. 53. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-OX40 antibody. 236 Attorney Docket No.45817-0192WO1 / MTX1067.20 54. The method of claim 53, wherein the agonist anti-OX40 antibody is tavolimab, MOXR-0916, PF-04518600, GSK3174998, BMS-986178, INCAGN01949, or 9B12. 55. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-CD27 antibody. 56. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-4-1BB antibody. 57. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-GITR antibody. 58. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist of an immune checkpoint molecule. 59. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-PD-1antibody. 60. The method of claim 59, wherein the antagonist anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, sintilimab, retifanlimab, AB122, AMP-224, JTX-4014, BGB-108, BCD-100, BAT1306, LZM009, AK105, HLX10, or TSR-042. 61. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-PD-L1 antibody. 62. The method of claim 61, wherein the antagonist anti-PD-L1 antibody is atezolizumab, avelumab, durvalumab, tislelizumab, BMS-935559, MEDI4736, FAZ053, 237 Attorney Docket No.45817-0192WO1 / MTX1067.20 KN035, CS1001, SHR-1316, CBT-502, A167, STI-A101, CK-301, BGB-A333, MSB- 2311, HLX20, or LY3300054. 63. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-CTLA-4 antibody. 64. The method of claim 63, wherein the antagonist anti-CTLA-4 antibody is ipilimumab, tremelimumab, AGEN1884, or CP-675,206. 65. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-LAG-3 antibody. 66. The method of claim 65, wherein the antagonist anti-LAG-3 antibody is relatlimab, LAG525, or INCAGN2385. 67. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-PD-L2 antibody. 68. A composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a polypeptide comprising an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1-7, 16-26, or 28-29. 69. A polypeptide comprising an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1-7, 16-26, or 28- 29. 238