[go: up one dir, main page]

WO1999022763A2 - Immunomodulateurs encapsules utilises comme adjuvants de vaccins - Google Patents

Immunomodulateurs encapsules utilises comme adjuvants de vaccins Download PDF

Info

Publication number
WO1999022763A2
WO1999022763A2 PCT/US1998/023313 US9823313W WO9922763A2 WO 1999022763 A2 WO1999022763 A2 WO 1999022763A2 US 9823313 W US9823313 W US 9823313W WO 9922763 A2 WO9922763 A2 WO 9922763A2
Authority
WO
WIPO (PCT)
Prior art keywords
composition
immunomodulator
encapsulated
vaccine
composition according
Prior art date
Application number
PCT/US1998/023313
Other languages
English (en)
Other versions
WO1999022763A3 (fr
Inventor
Richard S. Dondero
Bruce C. Galton
Leslie S. Casey
Original Assignee
Cistron Biotechnology, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cistron Biotechnology, Inc. filed Critical Cistron Biotechnology, Inc.
Priority to IL13548098A priority Critical patent/IL135480A0/xx
Priority to CA002307541A priority patent/CA2307541A1/fr
Priority to EP98955231A priority patent/EP1027071A2/fr
Priority to AU12084/99A priority patent/AU1208499A/en
Priority to JP2000518694A priority patent/JP2001521908A/ja
Publication of WO1999022763A2 publication Critical patent/WO1999022763A2/fr
Publication of WO1999022763A3 publication Critical patent/WO1999022763A3/fr
Priority to AU2003200723A priority patent/AU2003200723B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2006—IL-1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55522—Cytokines; Lymphokines; Interferons
    • A61K2039/55527—Interleukins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55522—Cytokines; Lymphokines; Interferons
    • A61K2039/55527—Interleukins
    • A61K2039/55533—IL-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55522—Cytokines; Lymphokines; Interferons
    • A61K2039/55527—Interleukins
    • A61K2039/55538—IL-12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers

Definitions

  • the immune system is regulated in part by a complex network of chemical signals. These signals include the interleukins such as IL-l ⁇ and IL-l ⁇ .
  • IL-l ⁇ is a polypeptide hormone synthesized and secreted by stimulated monocytes.
  • the initial translation product of IL-l ⁇ is a 31 kDa precursor polypeptide having relatively low biological activity. After synthesis, the 31 kDa precursor for IL-l ⁇ is enzymatically cleaved to its highly active mature form which has a size of about 17.5 kDa.
  • the N- terminus of mature IL-l ⁇ derived from human activated monocytes has been characterized by an N-terminal amino acid sequence beginning with Ala-Pro.
  • the N- terminal Ala residue of human mature IL- 1 ⁇ is in the 117 position and an Asp residue is in the 116 position counting from the N-terminus of human precursor IL-1 ⁇ polypeptide.
  • Mature IL-l ⁇ consists of the C-terminal 153 residues of the precursor polypeptide.
  • IL-l ⁇ biological activity is often determined by assaying for stimulation of thymocyte proliferation.
  • IL-l ⁇ activities include stimulation of B-lymphocyte maturation, lymphocyte proliferation, stimulation of fibroblast growth and induction of acute-phase protein synthesis by hepatocytes.
  • IL-l ⁇ polypeptides Other biological activities have been attributed to IL-l ⁇ polypeptides. These include control of differentiation and activation of lymphocytes, stimulation of lymphokine and prostaglandin production, promotion of inflammation, induction of acute phase proteins, stimulation of bone resorption, and alteration of the level of iron and zinc in blood. Moreover, it has been found that IL-l ⁇ can stimulate the hypothalamus- pituitary-adrenal axis, suggesting that IL-l ⁇ is integrated in the complex neuroendocrine network that controls homeostasis. Maturation and release of mature IL-l ⁇ from macrophages does not proceed by conventional means normally associated with most secretory proteins because the precursor IL-l ⁇ polypeptide lacks a hydrophobic signal sequence.
  • IL-l ⁇ is not associated with a membrane-bound compartment in monocytes.
  • Most secretory proteins .are characterized by the presence of a hydrophobic stretch of amino acids called a signal sequence.
  • the signal sequence directs the translocation of the protein across the membrane of the endoplasmic reticulum during protein synthesis. The protein is subsequently ushered out of the cell via exocytosis.
  • Most secreted proteins have a signal sequence at the amino terminal that is removed upon translocation.
  • Other proteins, such as ovalbumin have an internal signal sequence that is not removed upon translocation.
  • the precursor form of IL-l ⁇ lacks any region (either amino terminal or internal) with sufficient hydrophobicity and length to qualify as a signal sequence.
  • Microencapsulation is the process of enveloping certain drags, enzymes, toxins, or other substances in polymeric matrices. It can be used in controlled release or delayed release of drugs.
  • the many applications for encapsulation, the available matrices, and techniques for making and using encapsulation matrices are extensively covered elsewhere (see, for example, Chang, T.M.S. [1977] Biomedical applications of immobilized enzymes and proteins, Vols. 1-2, New York, Plenum Press; Deasy, P.B. (ed.) [1984] "Microencapsulation and related drug processes," In J. Swarbrick (ed.), Drugs and the pharmaceutical sciences: Vol. 20. Microencapsulation and related drug processes, New York: Marcel Dekker, Inc.; McGinity, J.W. [1989] "Aqueous polymeric coatings for pharmaceutical dosage forms," Drugs and the Pharmaceutical Sciences 36;
  • U.S. Patent No. 4,832,686 discloses the microencapsulation of IL-2 in a biocompatible polymer formulation.
  • Liposomes are closed structures that have a lipid bilayer membrane that can be used to encapsulate substances.
  • the liposomes can be prepared using standard materials and methods well known in the art.
  • U.S. Patent No. 5,059,421 discloses methods for preparing targeted liposomes of a defined size distribution.
  • an adjuvant in broad terms, may be thought of as a compound or composition which can enhance or amplify an animal's immune response (e.g., an increase in antibody titer) to an antigen or immunogen.
  • Various adjuvants are known in the art, including Freund's (complete and incomplete), muramyl dipeptide (MDP), and alum. More recently, polypeptides and small peptides have been used as adjuvants.
  • U.S. Patent No. 5,503,841 discloses the use of interleukin-2 (IL-2) as an adjuvant with vaccines.
  • U.S. Patent No. 5,206,014 discloses the use of a peptide fragment of human IL-l ⁇ as an adjuvant with antigens having low immunogenicity.
  • systemic administration of immunomodulators, such as IL-2, as adjuvants can result in an overstimulation or dysfunctional activation of the immune system of the animal.
  • compositions of the subject invention are immunomodulators encapsulated within a matrix.
  • the immunomodulators may be, for example, cytokines or lymphokines.
  • interleukin compounds such as IL- 1 ⁇ and/or
  • IL-l ⁇ are utilized according to the subject invention.
  • the subject invention provides adjuvant compositions comprising encapsulated IL-l ⁇ .
  • the encapsulated IL-l ⁇ composition can optionally include a vaccine antigen, such as whole inactivated or attenuated virus, recombinant or synthetic peptides, and other antigenic materials.
  • a vaccine antigen such as whole inactivated or attenuated virus, recombinant or synthetic peptides, and other antigenic materials.
  • Use of encapsulated IL-l ⁇ permits presentation of IL-l ⁇ to antigen presenting cells with minimal systemic exposure.
  • the present invention also pertains to the use of encapsulated immunomodulators for use as a means to increase immune responses in a patient.
  • encapsulated IL-l ⁇ or IL-l ⁇ can be used as the immunomodulator for increasing immune responses.
  • encapsulated IL-l ⁇ is used as an adjuvant to stimulate or increase an immune response to an immunogen or antigen, such as those used in vaccine preparations.
  • the encapsulated immunomodulator of the subject invention can be administered in the presence or absence of a vaccine antigen.
  • the antigen can be encapsulated with the immunomodulator or it can be administered in a composition external to the encapsulated immunomodulator.
  • the encapsulated immunomodulator of the subject invention can be administered either prior to or subsequent to vaccine antigen administration.
  • Figure 1 shows anti-influenza A IgG antibody titer obtained after immunization of rats with the one of the following: influenza A/Beijing H 3 N 3 vaccine mixed with mature IL-l ⁇ (no encapsulation), influenza A/Beijing H 3 N 3 vaccine alone (no encapsulation), or influenza A/Beijing H 3 N 3 vaccine and mature IL-l ⁇ encapsulated together in liposomes.
  • SEQ ID NO. 1 is an amino acid sequence of human mature IL-l ⁇ .
  • the subject invention pertains to novel compositions comprising an encapsulated immunomodulator for the use as an adjuvant.
  • an interleukin compound such as IL-l ⁇ or IL-l ⁇
  • the immunomodulator is IL-l ⁇ .
  • the encapsulated IL-1 ⁇ compositions can be used as an adjuvant.
  • Encapsulated immunomodulator compositions of the present invention can optionally include or be used in conjunction with a vaccines, such as whole inactivated or attenuated viras, recombinant or synthetic polypeptides or peptides, haptens, and other antigenic or immunogenic materials.
  • a vaccines such as whole inactivated or attenuated viras, recombinant or synthetic polypeptides or peptides, haptens, and other antigenic or immunogenic materials.
  • Using the methods and materials of the present invention provides for presentation of IL-l ⁇ , either in the presence or absence of a vaccine, to antigen presenting cells of the immune system but with minimal systemic exposure of the patient to IL-l ⁇ .
  • IL-l ⁇ is used as the immunomodulator. More preferably, the IL-l ⁇ used with the present invention is human IL-l ⁇ .
  • the IL-1 ⁇ can be either in precursor form or mature form.
  • the IL-l ⁇ can be human mature IL-l ⁇ , or a biologically active fragment or variant thereof, when the encapsulated IL-l ⁇ is to be administered to a human.
  • the IL-l ⁇ used with the present invention has the amino acid sequence shown in SEQ ID NO. 1.
  • IL-l ⁇ from other animal species can be also be used when the present invention is administered to non-human species.
  • the IL- l ⁇ can be isolated from animal cells, synthesized, or produced by recombinant gene expression means.
  • additional molecules and/or immunomodulators such as cytokines, interleukins and biologically active peptides are also encapsulated with an immunomodulator of the present invention or are administered in conjunction with the present invention.
  • IL-l and/or IL-l ⁇ is a first immunomodulator which is encapsulated along with a second, different immunomodulator.
  • IL-2, IL-4, IL-12, and others can be encapsulated along with IL-l ⁇ and/or IL-l ⁇ .
  • Other suitable molecules are known in the art which the skilled artisan would understand as being useful in the subject invention.
  • Immunomodulators can be incorporated into an encapsulation matrix using methods known in the art.
  • the encapsulation matrix can be natural or synthetic.
  • an immunomodulator such as IL-l ⁇ can be incorporated in a biocompatible polymer material such as lactic acid, glycolide and glutamic acid.
  • the encapsulation matrix is a liposome.
  • the liposomes may be produced by any of the standard liposome preparation techniques which .are well known and readily carried out by those skilled in the art. Such liposome preparation techniques are described in, for example, U.S. Patent No. 5,252,348.
  • Immunomodulators can be encapsulated in the matrix in a suitable buffer or carrier solution.
  • the encapsulation matrix can also include molecules that target the encapsulated materials to specific tissues or cell types, e.g., .antigen presenting cells.
  • liposomes can have receptor molecules in the lipid bilayer for targeting to specific desired cells.
  • liposomes can have the Fc portion of immunoglobulin incorporated in the lipid bilayer for targeting to cells which express Fc receptors on their surface.
  • the encapsulation matrix may contain antibodies that are immunoreactive with a molecule expressed on the surface of a target cell (e.g., antibodies to MHC class II molecules can be used to target antigen presenting cells).
  • Antigen presenting cells can include mononuclear phagocytes, B lymphocytes, dendritic cells, Langerhans cells and endothelial cells.
  • the immunomodulator can also be incorporated in an encapsulation matrix that provides for controlled and/or continuous release of the immunomodulator once administered to a patient.
  • the IL-l ⁇ , or IL-l ⁇ , or other immunomodulator may be encapsulated in a matrix which provides for continuous release over time.
  • the matrix may be specifically adapted to release the immunomodulator upon some event such as a change in pH which results from a local infection. See, for example, U.S. Patent No. 5,554,147 for a description of pH sensitive biopolymers.
  • the subject invention also concerns methods for enhancing immune responses in an animal or human by administering an effective amount of encapsulated of an encapsulated immunomodulator to the person or animal in need of such treatment.
  • encapsulated IL-l ⁇ can be used as an adjuvant to increase immune responses to an immunogen or antigen, such as those used in vaccine compositions.
  • the vaccine composition can comprise whole inactivated or attenuated viras, subunits of viral components, recombinant or synthetic polypeptides or peptides, haptens, and other antigenic or immunogenic materials.
  • the encapsulated IL- l ⁇ can be administered in the presence or absence of a vaccine composition.
  • the encapsulated IL-l ⁇ is administered in a pharmaceutically acceptable carrier.
  • the vaccine composition can be encapsulated together with IL-1 ⁇ or it can be administered in a composition external to the encapsulated IL-l ⁇ .
  • the encapsulated IL-l ⁇ of the subject invention can also be administered either prior to or subsequent to vaccine administration.
  • the amount of IL-l ⁇ or other immunomodulator to be administered according to the subject methods of the invention can be readily determined by a person skilled in the art having the benefit of the instant disclosure.
  • the encapsulated compositions of the present invention can be administered to an animal or human parenterally, for example, by intramuscular or subcutaneous injection.
  • compositions of the present invention can be used with vaccines directed to treating or immunizing animals and/or humans against bacteria, viruses, tumor cells, fungus, and parasites.
  • Example 1 Encapsulation of IL-l ⁇ and Vaccine Experiment.
  • This investigation employed four groups of female Sprague-Dawley rats. The investigation was for 58 days and the purpose was to evaluate the use of IL-l ⁇ as an adjuvant.
  • the vaccine used for these experiments was influenza A/Beijing H 3 N 3 (Parke Davis). Each animal's weight was recorded prior to dosing on Day 0, and then animals were administered 100 microliters of a sample comprising liposome encapsulated IL-l ⁇ intramuscularly. Thereafter, the animals were reweighed and their weight recorded every seven days prior to their blood being drawn for the duration of the study. On day 30, animals were administered a booster dose of the test sample. Blood was collected on days 0, 7, 14, 28, 37, and 58 for determining serum IgG ELISA titers. Animals were observed daily for sickness or mortality. On day 58, the rats were weighed and euthanized.
  • the encapsulated immunomodulator compositions described herein can be advantageously used in conjunction with an antigenic or immunogenic composition for the preparation of a vaccine.
  • Such a composition when administered to a person or animal, increases immune responses to the administered vaccine antigen as compared to vaccine antigen when administered alone.
  • Vaccines can be prepared by procedures well known in the art.
  • such vaccines can be prepared as injectables, e.g., liquid solutions or suspensions.
  • Solid forms for solution in, or suspension in, a liquid prior to injection also can be prepared.
  • the preparation also can be emulsified.
  • the encapsulated immunomodulator compositions and active antigenic ingredient or ingredients can be mixed with excipients which are pharmaceutically acceptable and compatible with the active ingredient.
  • excipients are water, saline, dextrose, glycerol, ethanol, or the like, and combinations thereof.
  • the vaccine can contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, or adjuvants such as aluminum hydroxide or muramyl dipeptide or variations thereof.
  • cholera toxin subunit B or other agents which stimulate antibody production at mucosal sites can be used.
  • Vaccines are conventionally administered parenterally, by injection, for example, either subcutaneously or intramuscularly. Additional formulations which are suitable for other modes of administration include suppositories and, in some cases, oral formulations.
  • suppositories traditional binders and carriers include, for example, polyalkalene glycols or triglycerides. Suppositories can be formed from mixtures containing the active ingredient in the range of about 0.5% to about 10%, preferably about 1 to about 2%.
  • Oral formulations can include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like. These compositions can take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain from about 10% to about 95% of active ingredient, preferably from about 25% to about 70%.
  • the compounds can be formulated into the vaccine as neutral or salt forms.
  • Pharmaceutically acceptable salts include the acid addition salts (formed with the free amino groups of the peptide) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine, and the like.
  • a vaccine of the subject invention can be administered in a manner compatible with the dosage formulation, and in such amount as will be therapeutically effective .and immunogenic.
  • the quantity to be administered can depend on the subject to be treated and the degree of protection desired.
  • methods known to promote mucosal immunity can be combined with systemic immunity promoters to maximize immune responses. Suitable regimes for initial administration and booster shots are also variable, but are typified by an initial administration followed in one or two week intervals by a subsequent injection or other administration.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dispersion Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne des compositions comprenant un immunomodulateur encapsulé, tel que des cytokines et des lymphokines, qui est utilisé comme adjuvant pour stimuler une réponse immunitaire lorsqu'il est administré à un être humain ou à un animal. Par exemple, une lymphokine telle que l'IL-1α ou l'IL-1β peut être utilisée comme immunomodulateur encapsulé dans une matrice de la présente invention. La composition encapsulée peut comprendre un antigène de vaccin, tel qu'un virus entier inactivé ou atténué, des peptides recombinés ou synthétiques et d'autres matériaux antigéniques. La matrice d'encapsulation peut être naturelle ou synthétique. La présente invention concerne également l'utilisation, chez un être humain ou un animal, d'un immunomodulateur encapsulé comme adjuvant dans le but de stimuler les réponses immunitaires à un antigène ou à un autre matériau envers lequel on désire provoquer une réponse immunitaire.
PCT/US1998/023313 1997-10-31 1998-11-02 Immunomodulateurs encapsules utilises comme adjuvants de vaccins WO1999022763A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
IL13548098A IL135480A0 (en) 1997-10-31 1998-11-02 Encapsulated immunomodulators useful as vaccine adjuvants
CA002307541A CA2307541A1 (fr) 1997-10-31 1998-11-02 Immunomodulateurs encapsules utilises comme adjuvants de vaccins
EP98955231A EP1027071A2 (fr) 1997-10-31 1998-11-02 Immunomodulateurs encapsules utilises comme adjuvants de vaccins
AU12084/99A AU1208499A (en) 1997-10-31 1998-11-02 Encapsulated immunomodulators useful as vaccine adjuvants
JP2000518694A JP2001521908A (ja) 1997-10-31 1998-11-02 ワクチンアジュバントとして有用な封入された免疫調節物質
AU2003200723A AU2003200723B2 (en) 1997-10-31 2003-02-28 Encapsulated immunomodulators useful as vaccine adjuvants

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US96240797A 1997-10-31 1997-10-31
US08/962,407 1997-10-31

Publications (2)

Publication Number Publication Date
WO1999022763A2 true WO1999022763A2 (fr) 1999-05-14
WO1999022763A3 WO1999022763A3 (fr) 1999-08-05

Family

ID=25505819

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/023313 WO1999022763A2 (fr) 1997-10-31 1998-11-02 Immunomodulateurs encapsules utilises comme adjuvants de vaccins

Country Status (6)

Country Link
EP (1) EP1027071A2 (fr)
JP (1) JP2001521908A (fr)
AU (1) AU1208499A (fr)
CA (1) CA2307541A1 (fr)
IL (1) IL135480A0 (fr)
WO (1) WO1999022763A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110182922A1 (en) * 2004-02-27 2011-07-28 Vax Consulting Peptides of il1 beta and tnf alpha and method of treatment using same
US8753647B2 (en) 2005-09-30 2014-06-17 Lipoxen Technologies Limited Liposomal vaccine compositions comprising a polysaccharide antigen and a protein adjuvant
US8815253B2 (en) 2007-12-07 2014-08-26 Novartis Ag Compositions for inducing immune responses

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049423A2 (fr) * 1996-06-24 1997-12-31 Yissum Research Development Company Of The Hebrew University Of Jerusalem Composition de vaccin contre la grippe encapsulee dans des liposomes et leur procede de fabrication

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3002213B2 (ja) * 1989-11-29 2000-01-24 帝国臓器製薬株式会社 ペプチドおよびこのペプチドを含有する薬剤
EP0604727A1 (fr) * 1992-12-31 1994-07-06 American Cyanamid Company Immunogénéité améliorée d'un vaccin par incorporation d'un cytocine dans un complexe immunostimulant contenant un antigène

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049423A2 (fr) * 1996-06-24 1997-12-31 Yissum Research Development Company Of The Hebrew University Of Jerusalem Composition de vaccin contre la grippe encapsulee dans des liposomes et leur procede de fabrication

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch, Week 9136 Derwent Publications Ltd., London, GB; Class B04, AN 91-262316 XP002104336 & JP 03 170498 A (TEIKOKU HORMONE MFG CO LTD), 24 July 1991 *
LIMOR C ET AL: "Characterization of PLGA microspheres for the controlled delivery of IL-1alpha for tumor immunotherapy" JOURNAL OF CONTROLLED RELEASE, vol. 43, no. 2-3, 18 January 1997, page 261-272 XP004069894 *
See also references of EP1027071A2 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110182922A1 (en) * 2004-02-27 2011-07-28 Vax Consulting Peptides of il1 beta and tnf alpha and method of treatment using same
US8632781B2 (en) * 2004-02-27 2014-01-21 Vaxconsulting Immunogenic compounds comprising peptides of IL1β
US8753647B2 (en) 2005-09-30 2014-06-17 Lipoxen Technologies Limited Liposomal vaccine compositions comprising a polysaccharide antigen and a protein adjuvant
US9750692B2 (en) 2005-09-30 2017-09-05 Lipoxen Technologies Limited Liposomal vaccine compositions comprising a polysaccharide antigen and a protein adjuvant
US8815253B2 (en) 2007-12-07 2014-08-26 Novartis Ag Compositions for inducing immune responses

Also Published As

Publication number Publication date
JP2001521908A (ja) 2001-11-13
WO1999022763A3 (fr) 1999-08-05
IL135480A0 (en) 2001-05-20
AU1208499A (en) 1999-05-24
CA2307541A1 (fr) 1999-05-14
EP1027071A2 (fr) 2000-08-16

Similar Documents

Publication Publication Date Title
Tsuji et al. Immunomodulatory effects of a plasmid expressing B7‐2 on human immunodeficiency virus‐1‐specific cell‐mediated immunity induced by a plasmid encoding the viral antigen
DE69927262T2 (de) Cd40 bindende antikörper und ctl peptide zur behandlung von tumoren
EP1198250B1 (fr) Utilisation de proteines hybrides fc pour ameliorer l'immunogeneicite d'antigenes proteique et peptidique
JP5519477B2 (ja) Ｔ１免疫応答とｔ２免疫応答との間で調節するためのワクチン
US20020090379A1 (en) Inducing antibody response against self-proteins with the aid of foreign t-cell epitopes
JP6466327B2 (ja) 免疫調節ワクチン
KR20070094663A (ko) 적합성이 높은 담체에 의한 경비 수송／면역화
SK3062001A3 (en) Method for down-regulating osteoprotegerin ligand activity
US6656462B2 (en) Interleukin-1 muteins useful as vaccine adjuvants
US20050002951A1 (en) Novel method of inducing antigen-specific t cells
KR20020026544A (ko) Ｇｄｆ-8 활성을 하향-조절하는 방법
EP2231180B1 (fr) Vaccin contre la maladie d'alzheimer
AU2002233560A1 (en) Vaccine
WO2002070711A1 (fr) Vaccin
AU2013255860A1 (en) Compositions
JP2002544170A (ja) 免疫応答を高めるための可溶性同時刺激分子の使用
JP2002538219A (ja) 癌及び高増殖性疾患治療用の組成物及び方法
US20030152581A1 (en) Compound and method for the prevention and/or the treatment of allergy
MXPA02005867A (es) Metodo para mejorar las respuestas inmunitarias a la vacuna del virus de herpes simple.
WO1999022763A2 (fr) Immunomodulateurs encapsules utilises comme adjuvants de vaccins
AU2003200723B2 (en) Encapsulated immunomodulators useful as vaccine adjuvants
EP1539232A1 (fr) Immunisation contre la ghreline autologue
US6355256B1 (en) Compositions containing a p53 derived protein or peptide, an adjuvant, and interleukin-12 and uses thereof
JP5227028B2 (ja) インターロイキン−２の中和能を有する免疫治療用製剤
WO1996010423A1 (fr) COMPOSITION CONTENANT UNE PROTEINE OU UN PEPTIDE DERIVE DE LA MOLECULE p53, UN ADJUVANT ET L'INTERLEUKINE-12, ET UTILISATION DE CETTE PREPARATION

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 135480

Country of ref document: IL

AK Designated states

Kind code of ref document: A2

Designated state(s): AU CA IL JP

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AU CA IL JP

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

WWE Wipo information: entry into national phase

Ref document number: 1998955231

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2307541

Country of ref document: CA

Ref country code: CA

Ref document number: 2307541

Kind code of ref document: A

Format of ref document f/p: F

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 518694

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 12084/99

Country of ref document: AU

WWP Wipo information: published in national office

Ref document number: 1998955231

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1998955231

Country of ref document: EP