Vaccines

Research

Jump to: Other

16 pages, 6013 KiB

Open AccessArticle

COVID-19 Vaccine Effectiveness Studies against Symptomatic and Severe Outcomes during the Omicron Period in Four Countries in the Eastern Mediterranean Region

by Manuela Runge, Zahra Karimian, Mehrnaz Kheirandish, Giulio Borghi, Natalie Wodniak, Kamal Fahmy, Carsten Mantel, Thomas Cherian, Zeinab Nabil Ahmed Said, Farid Najafi, Fatima Thneibat, Zia Ul-Haq, Sheraz Fazid, Iman Ibrahim Salama, Fatemeh Khosravi Shadmani, Ahmad Alrawashdeh, Shadrokh Sirous, Saverio Bellizzi, Amira Ahmed, Michael Lukwiya, Arash Rashidian and on behalf of the Consortium of Authors Show full author list Hide full author list

Vaccines 2024, 12(8), 906; https://doi.org/10.3390/vaccines12080906 - 10 Aug 2024

Viewed by 1087

Abstract

Vaccine effectiveness (VE) studies provide real-world evidence to monitor vaccine performance and inform policy. The WHO Regional Office for the Eastern Mediterranean supported a regional study to assess the VE of COVID-19 vaccines against different clinical outcomes in four countries between June 2021 [...] Read more.

Vaccine effectiveness (VE) studies provide real-world evidence to monitor vaccine performance and inform policy. The WHO Regional Office for the Eastern Mediterranean supported a regional study to assess the VE of COVID-19 vaccines against different clinical outcomes in four countries between June 2021 and August 2023. Health worker cohort studies were conducted in 2707 health workers in Egypt and Pakistan, of whom 171 experienced symptomatic laboratory-confirmed SARS-CoV-2 infection. Test-negative design case–control studies were conducted in Iran and Jordan in 4017 severe acute respiratory infection (SARI) patients (2347 controls and 1670 cases) during the Omicron variant dominant period. VE estimates were calculated for each study and pooled by study design for several vaccine types (BBIBP-CorV, AZD1222, BNT162b2, and mRNA-1273, among others). Among health workers, VE against symptomatic infection of a complete primary series could only be computed compared to partial vaccination, suggesting a benefit of providing an additional dose of mRNA vaccines (VE: 88.9%, 95%CI: 15.3–98.6%), while results were inconclusive for other vaccine products. Among SARI patients, VE against hospitalization of a complete primary series with any vaccine compared to non-vaccinated was 20.9% (95%CI: 4.5–34.5%). Effectiveness estimates for individual vaccines, booster doses, and secondary outcomes (intensive care unit admission and death) were inconclusive. Future VE studies will need to address challenges in both design and analysis when conducted late during a pandemic and will be able to utilize the strengthened capacities in countries. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Figure 1
Sample size flowchart for the (A) cohort studies and (B) TND studies. Vaccination status in cohort studies shown at start of follow-up. Full article ">Figure 2
Study population by vaccination status and time since vaccination over time. (A) Number of health workers in the two cohort studies by start of follow-up. The two vertical lines indicate start and end of study period. The grey shaded area indicates the pre-Omicron-dominant period. (B) Days since last vaccination and start of follow-up in the pooled cohort dataset (bottom) and corresponding density plot (top). The star symbol indicates outcome events during follow-up. (C) SARI patients in the two TND studies by admission date and vaccination status. (D) Days since vaccination and illness onset date in pooled TND studies (bottom) and corresponding density plot (top). Full article ">Figure 3
VE of a primary series and a booster compared to partial vaccination against lab-confirmed symptomatic COVID-19 infection among health workers compared to partial vaccination (reference). Blank VE estimates indicate insufficient data to be computed. Full article ">Figure 4
VE of a primary series and a booster compared to no vaccination against hospitalization among SARI patients. Blank VE fields indicate insufficient data to be computed. Full article ">Figure 5
VE of a primary series and a booster compared to no vaccination against ICU admission and/or death among SARI patients in the TND studies. Blank VE estimates indicate insufficient data to be computed. Full article ">

16 pages, 2787 KiB

Open AccessArticle

A Unique mRNA Vaccine Elicits Protective Efficacy against the SARS-CoV-2 Omicron Variant and SARS-CoV

by Xiaoqing Guan, Abhishek K. Verma, Gang Wang, Abhijeet Roy, Stanley Perlman and Lanying Du

Vaccines 2024, 12(6), 605; https://doi.org/10.3390/vaccines12060605 - 1 Jun 2024

Viewed by 1170

Abstract

The highly pathogenic coronaviruses SARS-CoV-2 and SARS-CoV have led to the COVID-19 pandemic and SARS outbreak, respectively. The receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2, particularly the Omicron variant, has frequent mutations, resulting in the reduced efficiency of current COVID-19 [...] Read more.

The highly pathogenic coronaviruses SARS-CoV-2 and SARS-CoV have led to the COVID-19 pandemic and SARS outbreak, respectively. The receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2, particularly the Omicron variant, has frequent mutations, resulting in the reduced efficiency of current COVID-19 vaccines against new variants. Here, we designed two lipid nanoparticle-encapsulated mRNA vaccines by deleting the mutant RBD of the SARS-CoV-2 Omicron variant (SARS2-S (RBD-del)) or by replacing this mutant RBD with the conserved and potent RBD of SARS-CoV (SARS2-S (SARS-RBD)). Both mRNA vaccines were stable at various temperatures for different time periods. Unlike SARS2-S (RBD-del) mRNA, SARS2-S (SARS-RBD) mRNA elicited effective T-cell responses and potent antibodies specific to both SARS-CoV-2 S and SARS-CoV RBD proteins. It induced strong neutralizing antibodies against pseudotyped SARS-CoV-2 and SARS-CoV infections and protected immunized mice from the challenge of the SARS-CoV-2 Omicron variant and SARS-CoV by significantly reducing the viral titers in the lungs after Omicron challenge and by completely preventing SARS-CoV-induced weight loss and death. SARS2-S (SARS-RBD)-immunized serum antibodies protected naïve mice from the SARS-CoV challenge, with its protective efficacy positively correlating with the neutralizing antibody titers. These findings indicate that this mRNA vaccine has the potential for development as an effective vaccine against current and future SARS-CoV-2 variants and SARS-CoV. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Figure 1
Construction and characterization of mRNA vaccines. (a) Construction of nucleoside-modified SARS2-S (SARS-RBD) and SARS2-S (RBD-del) mRNAs. Each of the synthesized mRNAs encodes tissue plasminogen activator (tPA) signal peptide (SP) and SARS-CoV-2 Omicron spike (S) protein with a deleted receptor-binding domain (RBD) or with the inserted SARS-CoV RBD, and contains a 5′ cap, 5′ untranslated region (UTR), 3′-UTR, and 3′ poly(A) tail. The synthesized mRNAs were formulated with lipid nanoparticles (LNPs) for vaccine delivery. (b) Detection of the stability of LNP-formulated mRNA vaccines or LNP control under different conditions. mRNA vaccines or control were stored at 4 °C, 25 °C, and 37 °C for 0, 24, 48, and 72 h, respectively, followed by measurement of particle sizes (hydrodynamic diameter) by DLS. (c) Western blot for detection of expression of mRNA-encoding protein. Each mRNA-LNP was incubated with 293T cells for 72 h at 37 °C and the culture supernature was tested by SARS2-S (SARS-RBD)-immunized mouse sera. kDa, protein molecular weight marker. (d) Representative figures of flow cytometry analysis of expression of mRNA-encoding protein. Each mRNA-LNP was incubated with 293T, A549, and Huh-7 cells, respectively, for 48 h at 37 °C, which were then stained with FITC-labeled mouse-anti-His antibody and measured for fluorescence intensity by flow cytometry. The grey-shaded region represents LNP-incubated cell controls. MFI indicates the Median Fluorescence Intensity. The data are expressed as mean ± standard deviation of the mean (s.e.m.) of triplicate wells. One experimental repeat was performed and similar results were obtained. Full article ">Figure 2
Evaluation of antibody responses and neutralizing antibodies induced by mRNA vaccines against infection of SARS-CoV-2 and SARS-CoV. (a) BALB/c mice were vaccinated with each mRNA vaccine, or LNP control, for a total of 3 times at 3-week intervals and bled 10 days post-last vaccination to test, by ELISA, for serum IgG antibodies targeting the RBD-deleted SARS-CoV-2 S (b) or SARS-CoV RBD (c) protein. These sera were also evaluated, by ELISA, for serum IgG1 subtype antibodies targeting the aforementioned SARS-CoV-2 S (d) or SARS-CoV RBD (e) protein, as well as for serum IgG2a subtype antibodies targeting the aforementioned SARS-CoV-2 S (f) or SARS-CoV RBD (g) protein. The SARS-CoV-2 S or SARS-CoV RBD protein was pre-coated to the ELISA plates and the respective antibody (Ab) titer was reported as mean ± s.e.m. (from five mice per group). The aforementioned mouse sera were also detected for neutralizing antibodies against pseudoviruses expressing the respective S proteins of SARS-CoV-2 ancestral strain (h) and the ancestral strain (Tor2) of SARS-CoV (i). The neutralizing antibody titer (NT50: 50% neutralizing Ab titer) is expressed as mean ± s.e.m. (from five mice per group). One experimental repeat was performed and similar results were obtained. Full article ">Figure 3
Evaluation of mRNA vaccine-induced T-cell responses. (a) BALB/c mice were immunized with each mRNA vaccine or LNP control for 3 times at 3-week intervals and splenocytes collected 2 months post-last vaccine dose were tested for cytokine expression by Multiplex assay. Isolated splenocytes were stimulated with RBD-deleted SARS-CoV-2 S (b) or SARS-CoV RBD (c) protein and the expressed cytokines (pg/mL) were measured in the supernatant. Significant differences among different groups are shown as * (p < 0.05), ** (p < 0.01), and *** (p < 0.001). The experiments were repeated once, resulting in similar results. Full article ">Figure 4
Evaluation of mRNA vaccine-induced protective efficacy against SARS-CoV-2 and SARS-CoV. (a) At a time of 40 days after the last immunization, BALB/c mice were i.n.-challenged with the SARS-CoV-2 Omicron variant (BA.1, 105 PFU/mL) and lungs were collected two days later to measure viral titers by plaque assay and viral replication by qRT-PCR. Evaluation of viral titers (b) and viral replication (c) in the lungs. The viral titers were reported as the PFU/mL of lung tissues. The viral (nucleocapsid gene) replication was normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The data are presented as mean ± s.e.m. (from five mice per group). One experimental repeat was performed and similar results were obtained. (d–h) In a separate experiment, vaccinated mice were challenged (i.n.) with the MA15 strain of SARS-CoV (500 PFU/mL) and investigated for survival and weight loss for 14 days after the virus challenge. The data (in (e) and (h)) are expressed as mean ± s.e.m. of three (for surviving mice in the LNP control group from day 9) to five mice (for mRNA vaccine groups and LNP control group by day 8) in each group. Significant differences among different groups are shown as * (p < 0.05), ** (p < 0.01), and *** (p < 0.001). Full article ">Figure 5
Evaluation of passive protective efficacy of mRNA vaccine-induced mouse serum antibodies. (a) Experimental procedure and challenge schedule. Naïve BALB/c mice were i.p.-injected with the pooled sera of mice receiving vaccines (SARS2-S (SARS-RBD) mRNA or SARS2-S (RBD-del) mRNA) or LNP control, i.n.-challenged with the heterologous SARS-CoV (MA15 strain, 400 PFU/mL) 12 h later, and measured for viral titers in the lungs by plaque assay two days post-challenge. (b) Evaluation of viral titers after serum transfer. The viral titers were expressed as the PFU/mL of lung tissues. The data are presented as mean ± s.e.m. (from five mice per group). ** (p < 0.01) and *** (p < 0.001) indicate significant differences among different groups. (c) Plaque reduction neutralization assay was tested for the aforementioned pooled mouse sera against infection of the heterologous authentic MA15 strain of SARS-CoV. The 50% neutralizing antibody (Ab) titer (NT50) was calculated and the data are expressed as mean ± s.e.m. (from duplicate wells of pooled sera per group). One experimental repeat was performed and similar results were obtained. Full article ">

21 pages, 570 KiB

Open AccessArticle

The Limitations of a Hypothetical All-Variant COVID-19 Vaccine: A Simulation Study

by Robert J. Kosinski

Vaccines 2024, 12(5), 532; https://doi.org/10.3390/vaccines12050532 - 13 May 2024

Viewed by 808

Abstract

This paper simulates a hypothetical pan-coronavirus vaccine that confers immediate sterilizing immunity against all SARS-CoV-2 variants. Simulations used a SEIIS (susceptible, exposed, infective, immune, susceptible) spreadsheet model that ran two parallel subpopulations: one that accepted vaccination and another that refused it. The two [...] Read more.

This paper simulates a hypothetical pan-coronavirus vaccine that confers immediate sterilizing immunity against all SARS-CoV-2 variants. Simulations used a SEIIS (susceptible, exposed, infective, immune, susceptible) spreadsheet model that ran two parallel subpopulations: one that accepted vaccination and another that refused it. The two subpopulations could transmit infections to one another. Using data from the United States (US), the simulated vaccine was tested against limiting factors such as vaccine hesitancy, slow vaccination distribution, and the development of high-transmission variants. The vaccine was often successful at reducing cases, but high-transmission variants and discontinuation of non-pharmaceutical interventions (NPIs) such as masking greatly elevated cases. A puzzling outcome was that if NPIs were discontinued and high-transmission variants became common, the model predicted consistently higher rates of disease than are actually observed in the US in 2024. However, if cumulative exposure to virus antigens increased the duration of immunity or decreased the infectivity of the virus, the model predictions were brought back into a more realistic range. The major finding was that even when a COVID-19 vaccine always produces sterilizing immunity against every SARS-CoV-2 variant, its ability to control the epidemic can be compromised by multiple common conditions. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

13 pages, 1551 KiB

Open AccessArticle

Comparative Analysis of Vaccine-Induced Neutralizing Antibodies against the Alpha, Beta, Delta, and Omicron Variants of SARS-CoV-2

by Philipp Girl, Heiner von Buttlar, Enrico Mantel, Markus H. Antwerpen, Roman Wölfel and Katharina Müller

Vaccines 2024, 12(5), 515; https://doi.org/10.3390/vaccines12050515 - 9 May 2024

Viewed by 1098

Abstract

The SARS-CoV-2 virus has infected more than 660 million people and caused nearly seven million deaths worldwide. During the pandemic, a number of SARS-CoV-2 vaccines were rapidly developed, and several are currently licensed for use in Europe. However, the optimization of vaccination regimens [...] Read more.

The SARS-CoV-2 virus has infected more than 660 million people and caused nearly seven million deaths worldwide. During the pandemic, a number of SARS-CoV-2 vaccines were rapidly developed, and several are currently licensed for use in Europe. However, the optimization of vaccination regimens is still ongoing, particularly with regard to booster vaccinations. At the same time, the emergence of new virus variants poses an ongoing challenge to vaccine efficacy. In this study, we focused on a comparative analysis of the neutralization capacity of vaccine-induced antibodies against four different variants of concern (i.e., Alpha, Beta, Delta, and Omicron) after two and three doses of COVID-19 vaccine. We were able to show that both two (prime/boost) and three (prime/boost/boost) vaccinations elicit highly variable levels of neutralizing antibodies. In addition, we did not observe a significant difference in antibody levels after two and three vaccinations. We also observed a significant decrease in the neutralization susceptibility of all but one SARS-CoV-2 variants to vaccine-induced antibodies. In contrast, a SARS-CoV-2 breakthrough infection between the second and third vaccination results in overall higher levels of neutralizing antibodies with a concomitant improved neutralization of all virus variants. Titer levels remained highly variable across the cohort but a common trend was observed. This may be due to the fact that at the time of this study, all licensed vaccines were still based exclusively on wild-type SARS-CoV-2, whereas infections were caused by virus variants. Overall, our data demonstrate the importance of (booster) vaccinations, but at the same time emphasize the need for the continued adaptation of vaccines to induce a protective immune response against virus variants in order to be prepared for future (seasonal) SARS-CoV-2 outbreaks. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Figure 1
Overview of nonsynonymous mutations within the genomes of the evaluated virus variants of concern (compared to NCBI Ref Seq NC_045512.2) ((A): MUC-IMB-1 (B): Alpha, (C): Beta, (D): Delta, and (E): Omicron BA.1). Full article ">Figure 2
Distribution of NAb titers against all tested variants after two (A) and three (B) vaccinations. Whiskers extend from minimum to maximum titer levels and all titers are shown Red line indicated the threshold of the NT. Apart from the exceptions indicated (ns), all titer differences between variants were statistically significant. While the neutralization sensitivity of the Alpha variant is largely maintained compared to WT, all other variants show a significant reduction in neutralization sensitivity after two and three vaccinations. The overall lowest titers can be observed against the Omicron variant, followed by the Beta and Delta variant. ((A): WT-Alpha: p = 0.18, WT-Beta: p = 0.0001, WT-Delta: p = 0.0001, and WT-Omicron: p = 0.0001; Alpha–Beta: p = 0.0001, Alpha–Delta: p = 0.0001, and Alpha–Omicron: p = 0.0001; Beta–Delta: p = 0.07 and Beta–Omicron: p = 0.0001; Delta–Omicron: p = 0.0001). ((B): WT-Alpha: p = 0.42, WT-Beta: p = 0.0001, WT-Delta: p = 0.009, and WT-Omicron: p = 0.0001; Alpha–Beta: p = 0.0001, Alpha–Delta: p = 0.0002, and Alpha–Omicron: p = 0.0001; Beta–Delta: p = 0.0001 and Beta–Omicron: p = 0.0001; Delta–Omicron: p = 0.0001). Full article ">Figure 3
Increased neutralization sensitivity of virus variants after confirmed breakthrough infection. (A) Mean NAb titers after two (●) and three (▲) vaccinations and after additional breakthrough infection (▪) reveal overall increased neutralization sensitivity of all virus variants against infection-induced Nab. (B) NAb titer developments of all ten triple-vaccinated patients with confirmed breakthrough infection (▲ patient 1, ● patient 2, ▪ patient 3, ▼ patient 4, ⨂ patient 5, ○ patient 6, ⬣ patient 7, ◇ patient 8, ⬥ patient 9, □ patient 10). Although the trends are very similar, the titer levels of the individual patients differ, sometimes considerably. Direct comparison of mean titers after two and three vaccinations reveals statistically significant titer differences for WT titers (103 vs. 62, p = 0.0036) and Beta titers (25 vs. 12, p = 0.0005). Full article ">Figure 4
Neutralizing capacity of sera against virus variants. Neutralization of virus variants by sera from patients with different vaccination histories was compared. (A) Depicted are the percentages of neutralizing sera (titer ≥ 5) against virus variants for each group. (B) Neutralizing titers were normalized to the neutralizing titer against WT by dividing individual titers by the mean titer of WT for every group. The means and standard deviations are depicted. Data were analyzed for multiple comparisons with unpaired t-test with Welch correction. Statistically significant differences are marked with * (p < 0.05). Full article ">

14 pages, 5294 KiB

Open AccessArticle

Evaluation of the Abdala Vaccine: Antibody and Cellular Response to the RBD Domain of SARS-CoV-2

by Lorenzo Islas-Vazquez, Yan Carlos Alvarado-Alvarado, Marisa Cruz-Aguilar, Henry Velazquez-Soto, Eduardo Villalobos-Gonzalez, Gloria Ornelas-Hall, Sonia Mayra Perez-Tapia and Maria C. Jimenez-Martinez

Vaccines 2023, 11(12), 1787; https://doi.org/10.3390/vaccines11121787 - 30 Nov 2023

Cited by 1 | Viewed by 2548

Abstract

Abdala is a recently released RBD protein subunit vaccine against SARS-CoV-2. A few countries, including Mexico, have adopted Abdala as a booster dose in their COVID-19 vaccination schemes. Despite that, most of the Mexican population has received full-scheme vaccination with platforms other than [...] Read more.

Abdala is a recently released RBD protein subunit vaccine against SARS-CoV-2. A few countries, including Mexico, have adopted Abdala as a booster dose in their COVID-19 vaccination schemes. Despite that, most of the Mexican population has received full-scheme vaccination with platforms other than Abdala; little is known regarding Abdala’s immunological features, such as its antibody production and T- and B-cell-specific response induction. This work aimed to study antibody production and the adaptive cellular response in the Mexican population that received the Abdala vaccine as a booster. We recruited 25 volunteers and evaluated their RBD-specific antibody production, T- and B-cell-activating profiles, and cytokine production. Our results showed that the Abdala vaccine increases the concentration of RBD IgG-specific antibodies. Regarding the cellular response, after challenging peripheral blood cultures with RBD, the plasmablast (CD19+CD27+CD38^High) and transitional B-cell (CD19+CD21+CD38^High) percentages increased significantly, while T cells showed an increased activated phenotype (CD3+CD4+CD25+CD69+ and CD3+CD4+CD25+HLA-DR+). Also, IL-2 and IFN-γ increased significantly in the supernatant of the RBD-stimulated cells. Our results suggest that Abdala vaccination, used as a booster, evokes antibody production and the activation of previously generated memory against the SARS-CoV-2 RBD domain. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
Experimental design. (A) Recruitment and selection of participants. Blood sample collection was conducted 1 day before Abdala vaccination, 14 ± 5 days post-Abdala vaccination, and after 6 months of follow-up, as indicated by the red marker. (B) Serum samples from pre-vaccination, 14 ± 5 days after post-Abdala vaccination and after 6 months of follow-up were employed for antibody consumption and ELISA. On the other hand, the blood sample collected in sodium heparin, 14 ± 5 days after Abdala vaccination, was employed for a stimulation assay and flow cytometry analysis. Created with BioRender.com. Full article ">Figure 2
Representative flow cytometry analysis. In an FSC-A vs. FSC-H dot plot, we excluded doublets. Then, the lymphocyte region was selected in an FSC-A vs. SSC-A dot plot. Next, an SSC-A vs. CD19 dot plot was made. From the gated-CD19 region, a CD27 vs. CD21 plot, a CD38 vs. CD21 plot, and a CD38 vs. CD27 plot were made. Conversely, an SSC-A vs. CD3 followed by CD3 vs. CD4 dot plot was made. From the gated-CD3+CD4+ region, a CD4 vs. CD25 plot, CD25 vs. CD69 plot, and CD25 vs. HLA-DR plot were made. Full article ">Figure 3
IgGs related to SARS-CoV-2 against RBD domain of S protein induced at distinct points in the vaccination schedule. (A) OD of IgG against RBD pre- and 14 ± 5 days post-Abdala vaccination and 6 months (6 m) post-Abdala vaccination. Pre-Abdala vaccination, n = 25; 14 ± 5 days post-Abdala vaccination, n = 25; and 6 months (6 m) post-Abdala vaccination, n = 17. (B) OD throughout vaccination scheme. Pre-vaccination (non-vaccinated), n = 34; first dose, n = 54; second dose, n = 44; booster dose, n = 12; 10 months after booster dose, n = 46; Abdala vaccination, n = 25; and 6 months (6 m) post-Abdala vaccination, n = 17. Cut-off values are indicated by lines. Mean and standard deviation (SD) are shown. Central trend values and dispersion values are indicated in <a href="#app1-vaccines-11-01787" class="html-app">Table S1 in Supplementary Data</a>. Full article ">Figure 4
Antibody consumption after 24 h incubated with and without RBD recombinant protein. OD of IgG against RBD pre- and 14 ± 5 days post-Abdala vaccination and six months post-Abdala vaccination. Pre-Abdala vaccination, n = 25; 14 ± 5 days post-Abdala vaccination, n = 25; and 6 months (6 m) post-Abdala vaccination, n = 17. Cut-off values are indicated by lines. Mean and standard deviation (SD) are shown. Central trend values and dispersion values are indicated in <a href="#app1-vaccines-11-01787" class="html-app">Table S2 in Supplementary Data</a>. Full article ">Figure 5
Analysis of B lymphocytes after stimulus with and without RBD protein for 24 h. (A) Percentage of resting-memory (CD19+CD21+CD27+) and activated–memory (CD19+CD21 − CD27+) B lymphocytes. (B) Percentage of plasmablast cells (CD19+CD27+CD38high). (C) Percentage of transitional B lymphocytes (CD19+CD21+CD38high). n = 25. Mean and standard deviation (SD) are shown. Central trend values and dispersion values are indicated in <a href="#app1-vaccines-11-01787" class="html-app">Table S3 in Supplementary Data</a>. Full article ">Figure 6
Analysis of T lymphocytes after stimulus with and without RBD protein for 24 h. (A) Percentage of CD3+CD4+CD25+ T lymphocytes gated on CD3+. (B) Percentage of CD3+CD4+CD25+CD69+ T lymphocytes gated on CD3+CD4+. (C) Percentage of CD3+CD4+CD25+ HLA-DR+ T lymphocytes gated on CD3+CD4+. n = 25. Mean and standard deviation (SD) are shown. Central trend values and dispersion values are indicated in <a href="#app1-vaccines-11-01787" class="html-app">Table S4 in Supplementary Data</a>. Full article ">Figure 7
Concentration of IL-2 and IFN-γ after stimulus with RBD protein for 24 h. (A) pg/mL of IL-2. (B) pg/mL of IFN-γ. n = 23. Mean and standard deviation (SD) are shown. Central trend values and dispersion values are indicated in <a href="#app1-vaccines-11-01787" class="html-app">Table S5 in Supplementary Data</a>. Full article ">

14 pages, 2392 KiB

Open AccessArticle

Profile and Outcomes of Hospitalized COVID-19 Patients during the Prevalence of the Omicron Variant According to the Brazilian Regions: A Retrospective Cohort Study from 2022

by Pedro Dutra Drummond, Daniel Bortot de Salles, Natália Satchiko Hojo de Souza, Daniela Carine Ramires Oliveira, Daniel Ludovico Guidoni and Fernanda Sumika Hojo de Souza

Vaccines 2023, 11(10), 1568; https://doi.org/10.3390/vaccines11101568 - 5 Oct 2023

Cited by 1 | Viewed by 1047

Abstract

We investigated the clinical–epidemiological profile and outcomes of COVID-19 patients hospitalized in 2022, during the Omicron variant/subvariant prevalence, in different Brazilian regions to identify the most vulnerable subgroups requiring special attention. Data from COVID-19 patients were extracted from the national Information System for [...] Read more.

We investigated the clinical–epidemiological profile and outcomes of COVID-19 patients hospitalized in 2022, during the Omicron variant/subvariant prevalence, in different Brazilian regions to identify the most vulnerable subgroups requiring special attention. Data from COVID-19 patients were extracted from the national Information System for Epidemiological Surveillance of Influenza (SIVEP-Gripe database), and analyses stratified by region and age group were conducted. The constructed dataset encompassed clinical–epidemiological information, intensive care unit admission, invasive and non-invasive ventilation requirements, vaccination status, and evolution (cure or death). It was observed that there were significant differences in the vaccination rates between regions, in the occurrence of unfavorable outcomes, and in the pattern of comorbidities in young patients. The north region had higher rates of unvaccinated patients and a lower percentage of those vaccinated with three doses in all age groups compared to other regions. The northeast region had the highest rates of patients admitted to the ICU for all age groups, while the north and northeast were the most affected by IMV requirements and in-hospital death in all age groups. This study showed that extended vaccination coverage, especially booster doses, can protect different population segments from developing severe disease since lower vaccination coverage was observed in regions with higher fatality rates. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Figure 1
Percentage of patients hospitalized during the prevalence of the Omicron variant/subvariants (1 January 2022–31 December 2022) vaccinated with 1, 2, and 3 doses and unvaccinated stratified by region and age group. Full article ">Figure 2
Outcomes of hospitalized patients during the prevalence of the Omicron variant/subvariants (1 January 2022–31 December 2022). Percentage values by region and age group. Full article ">Figure 3
In-hospital deaths of patients hospitalized during the prevalence of Omicron variant/subvariants (1 January 2022–31 December 2022). Percentage values by region, age group, and number of doses of COVID-19 vaccine. Full article ">Figure 4
Comorbidities presented by patients hospitalized with COVID-19 during the prevalence of Omicron variant/subvariants (1 January 2022–31 December 2022) by age group and region. Full article ">Figure 5
Adjusted relative risks of death presented by patients hospitalized with COVID-19 during the prevalence of Omicron variant/subvariants (1 January 2022–31 December 2022) stratified by region. Full article ">Figure 5 Cont.
Adjusted relative risks of death presented by patients hospitalized with COVID-19 during the prevalence of Omicron variant/subvariants (1 January 2022–31 December 2022) stratified by region. Full article ">

15 pages, 1132 KiB

Open AccessArticle

Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers—ORCHESTRA Project

by Ludovica Leomanni, Giulia Collatuzzo, Emanuele Sansone, Emma Sala, Giuseppe De Palma, Stefano Porru, Gianluca Spiteri, Maria Grazia Lourdes Monaco, Daniela Basso, Sofia Pavanello, Maria Luisa Scapellato, Francesca Larese Filon, Luca Cegolon, Marcella Mauro, Vittorio Lodi, Tiziana Lazzarotto, Ivan Noreña, Christina Reinkemeyer, Le Thi Thu Giang, Eleonóra Fabiánová, Jozef Strhársky, Marco Dell’Omo, Nicola Murgia, Lucía A. Carrasco-Ribelles, Concepción Violán, Dana Mates, Agripina Rascu, Luigi Vimercati, Luigi De Maria, Shuffield S. Asafo, Giorgia Ditano, Mahsa Abedini and Paolo Boffetta Show full author list Hide full author list

Vaccines 2023, 11(10), 1527; https://doi.org/10.3390/vaccines11101527 - 26 Sep 2023

Cited by 1 | Viewed by 1898

Abstract

Background: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). Methods: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 [...] Read more.

Background: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). Methods: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. Results: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00–1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29–2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97–1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91–0.98 per 30-day increase). Conclusions: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

13 pages, 1821 KiB

Open AccessArticle

Effectiveness of Mix-and-Match Vaccination in Preventing SARS-CoV-2 Omicron Variant Infection in Taiwan: A Test-Negative Control Study

by Yu-Tung Huang, Yi-Ching Chen, Chih-Hsien Chuang, Shang-Hung Chang and Cheng-Hsun Chiu

Vaccines 2023, 11(9), 1441; https://doi.org/10.3390/vaccines11091441 - 31 Aug 2023

Cited by 1 | Viewed by 2370

Abstract

This study aimed to evaluate the effectiveness (VE) of mix-and-match vaccination against SARS-CoV-2 Omicron variant infection and severe outcomes. An SARS-CoV-2 PCR-confirmed retrospective cohort from Chang Gung Medical System in Taiwan was constructed. Vaccination records were tracked from the National Immunization Information System [...] Read more.

This study aimed to evaluate the effectiveness (VE) of mix-and-match vaccination against SARS-CoV-2 Omicron variant infection and severe outcomes. An SARS-CoV-2 PCR-confirmed retrospective cohort from Chang Gung Medical System in Taiwan was constructed. Vaccination records were tracked from the National Immunization Information System and categorized by different regimens or unvaccinated status. The main outcomes are VE against PCR-confirmed infection and COVID-19-associated moderate to severe disease. Participants were observed during the Omicron wave from March to August 2022. Of 298,737 PCR testing results available, 162,219 were eligible for analysis. VE against infection was modest, ranging from 38.3% to 49.0%, while mRNA-based vaccine regimens revealed better protection against moderate to severe disease, ranging from 80.8% to 90.3%. Subgroup analysis revealed lower VE among persons with major illness in preventing moderate to severe disease. For young adults, the VE of protein-based vaccine regimens showed a comparable protection with other mixed vaccine regimens. The mix-and-match vaccination strategy provided modest clinical effectiveness in preventing Omicron variant infection. mRNA vaccine-based regimens were superior to other regimens against moderate to severe disease especially in older adults. The mix-and-match vaccination strategy could be an alternative to prevent COVID-19 in unstable vaccine supply regions. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Figure 1
Study population and algorithm. Note: The data used in the study were retrieved from the Chang Gung Research Database (CGRD) and the National Immunization Information System (NIIS) dataset between 1 March and 31 August 2022 in Taiwan. Full article ">Figure 2
Forest plot of vaccine effectiveness against SARS-CoV-2 Omicron variant infection and COVID-19-associated moderate to severe disease. (a,b) show the effectiveness against SARS-CoV-2 Omicron variant infection and COVID-19-associated moderate to severe disease, respectively. Note: The vaccine effectiveness and 95% confidence intervals for each group were estimated as one minus the adjusted hazard ratio and are presented as a percentage. VE stands for vaccine effectiveness and C.I. for confidence interval. Abbreviations: A, ChAdOx1 nCOV-19; M, mRNA-1273; B, BNT162b2; MVC, MVC-COV1901. Full article ">Figure 3
Subgroup analysis of the vaccine effectiveness against Omicron variant infection and COVID-19-associated moderate to severe disease. (a) shows effectiveness against Omicron variant infection in persons without underlying major illness, (b) shows effectiveness against Omicron variant infection in persons with major illness, (c) shows effectiveness against COVID-19-associated moderate to severe disease in persons without major illness, and (d) shows effectiveness against COVID-19-associated moderate to severe disease in persons with major illness. Note: The vaccine effectiveness and 95% confidence intervals for each group were estimated as one minus the adjusted hazard ratio and are presented as a percentage. VE stands for vaccine effectiveness and C.I. for confidence interval. Abbreviations: A, ChAdOx1 nCOV-19; M, mRNA-1273; B, BNT162b2; MVC, MVC-COV1901. Full article ">

16 pages, 3865 KiB

Open AccessArticle

Phenotypic Changes in T and NK Cells Induced by Sputnik V Vaccination

by Anna A. Boyko, Maria O. Ustiuzhanina, Julia D. Vavilova, Maria A. Streltsova, Sofya A. Kust, Andrei E. Siniavin, Irina V. Astrakhantseva, Marina S. Drutskaya and Elena I. Kovalenko

Vaccines 2023, 11(6), 1047; https://doi.org/10.3390/vaccines11061047 - 31 May 2023

Viewed by 1658

Abstract

A highly effective humoral immune response induced by the Sputnik V vaccine was demonstrated in independent studies, as well as in large-scale post-vaccination follow-up studies. However, the shifts in the cell-mediated immunity induced by Sputnik V vaccination are still under investigation. This study [...] Read more.

A highly effective humoral immune response induced by the Sputnik V vaccine was demonstrated in independent studies, as well as in large-scale post-vaccination follow-up studies. However, the shifts in the cell-mediated immunity induced by Sputnik V vaccination are still under investigation. This study was aimed at estimating the impact of Sputnik V on activating and inhibitory receptors, activation and proliferative senescence markers in NK and T lymphocytes. The effects of Sputnik V were evaluated by the comparison of PBMC samples prior to vaccination, and then three days and three weeks following the second (boost) dose. The prime-boost format of Sputnik V vaccination induced a contraction in the T cell fraction of senescent CD57⁺ cells and a decrease in HLA-DR-expressing T cells. The proportion of NKG2A⁺ T cells was down-regulated after vaccination, whereas the PD-1 level was not affected significantly. A temporal increase in activation levels of NK cells and NKT-like cells was recorded, dependent on whether the individuals had COVID-19 prior to vaccination. A short-term elevation of the activating NKG2D and CD16 was observed in NK cells. Overall, the findings of the study are in favor of the Sputnik V vaccine not provoking a dramatic phenotypic rearrangement in T and NK cells, although it induces their slight temporal non-specific activation. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Other

Jump to: Research

9 pages, 708 KiB

Open AccessBrief Report

SARS-CoV-2 Humoral Immunity Persists Following Rituximab Therapy

by Liangjian Lu, Chang Yien Chan, Yi Yang Lim, Mya Than, Sharon Teo, Perry Y. W. Lau, Kar Hui Ng and Hui Kim Yap

Vaccines 2023, 11(12), 1864; https://doi.org/10.3390/vaccines11121864 - 18 Dec 2023

Cited by 2 | Viewed by 1315

Abstract

Long-term humoral immunity is mediated by short-lived plasma cells (replenished by memory B cells) and long-lived plasma cells. Their relative contributions are uncertain for immunity to SARS-CoV-2, especially given the widespread use of novel mRNA vaccines. Yet, this has far-reaching implications in terms [...] Read more.

Long-term humoral immunity is mediated by short-lived plasma cells (replenished by memory B cells) and long-lived plasma cells. Their relative contributions are uncertain for immunity to SARS-CoV-2, especially given the widespread use of novel mRNA vaccines. Yet, this has far-reaching implications in terms of the need for regular booster doses in the general population and perhaps even revaccination in patients receiving B cell-depleting therapy. We aimed to characterise anti-SARS-CoV-2 antibody titres in patients receiving Rituximab following previous SARS-CoV-2 vaccination. We recruited 10 fully vaccinated patients (age: 16.9 ± 2.52 years) with childhood-onset nephrotic syndrome, not in relapse, receiving Rituximab for their steroid/calcineurin-inhibitor sparing effect. Antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins were measured immediately prior to Rituximab and again ~6 months later, using the Roche Elecys^® Anti-SARS-CoV-2 (S) assay. All ten patients were positive for anti-S antibodies prior to Rituximab, with six patients (60%) having titres above the upper limit of detection (>12,500 U/mL). Following Rituximab therapy, there was a reduction in anti-S titres (p = 0.043), but all patients remained positive for anti-S antibodies, with five patients (50%) continuing to have titres >12,500 U/mL. Six patients (60%) were positive for anti-N antibodies prior to Rituximab. Following Rituximab therapy, only three of these six patients remained positive for anti-N antibodies (p = 0.036 compared to anti-S seroreversion). Humoral immunity to SARS-CoV-2 is likely to be mediated in part by long-lived plasma cells. Full article

(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Immune Effectiveness of COVID-19 Vaccines

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (10 papers)

Research

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI