Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort.

Objective: In the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination. Methods: Volunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers. Results: Samples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p<0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age. Conclusion: The response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.

COVID-19 vaccine acceptance among adults in four major US metropolitan areas and nationwide.

This study assesses attitudes towards COVID-19 vaccination and the predictive value of COVID-VAC, a novel scale, among adults in the four largest US metropolitan areas and nationally. A 36-item survey of 6037 Americans was conducted in mid-April 2021. The study reports factors for COVID-19 vaccine acceptance among: (1) already vaccinated; (2) unvaccinated but willing to accept a vaccine; and (3) unvaccinated and unwilling to vaccinate. More than 20% were unwilling to vaccinate, expressing concerns about vaccine efficacy and safety and questioning the disease's severity. Poverty, working outside of the home and conservative political views are predictors of unwillingness. Conversely, those who either personally tested positive for COVID-19, or had a family member who did so, were more likely to accept vaccination. Majorities of all respondents supported vaccination mandates for employees and university students. Respondents preferred to receive vaccines in their doctor´s office. Lower income and conservative ideology, but not race, were strongly associated with vaccine unwillingness. The predictive value of COVID-VAC was demonstrated. While vaccination mandates are likely to be accepted, additional effective, targeted interventions to increase vaccine uptake are needed urgently.

Messages that increase COVID-19 vaccine acceptance: Evidence from online experiments in six Latin American countries.

As safe and effective vaccines become widely available, attaining herd immunity and limiting the spread of COVID-19 will depend on individuals choosing to vaccinate-and doing so quickly enough to outpace mutations. Using online surveys conducted across six Latin American countries in January 2021, we experimentally assess messages designed to counteract informational deficiencies and collective action problems that may drive hesitancy. We first find that basic vaccine information persuades around 8% of hesitant individuals to become willing to vaccinate, reduces intended wait to vaccinate by 0.4 months, and increases willingness to encourage others to vaccinate. Rather than facilitating free riding, learning, or social conformity, additional information about others' behavior increases vaccine acceptance when respondents expect herd immunity will be achieved. Finally, priming the social approval benefits of vaccinating also increases vaccine acceptance. These results suggest that providing information and shaping social expectations and incentives could both significantly increase vaccine uptake.

Mathematical Modeling of Vaccines That Prevent SARS-CoV-2 Transmission.

SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VEDIS), the ability to block symptomatic COVID-19. They only partially discriminate whether VEDIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VESUSC), or by preventing symptoms despite infection (VESYMP). Vaccine efficacy against transmissibility given infection (VEINF), the decrease in secondary transmissions from infected vaccine recipients, is also not measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna (mRNA-1273QS) and Pfizer-BioNTech (BNT162b2) vaccines, which demonstrated VEDIS > 90% in clinical trials, mediate VEDIS by VESUSC, then a limited fourth epidemic wave of infections with the highly infectious B.1.1.7 variant would have been predicted in spring 2021 assuming rapid vaccine roll out. If high VEDIS is explained by VESYMP, then high VEINF would have also been necessary to limit the extent of this fourth wave. Vaccines which completely protect against infection or secondary transmission also substantially lower the number of people who must be vaccinated before the herd immunity threshold is reached. The limited extent of the fourth wave suggests that the vaccines have either high VESUSC or both high VESYMP and high VEINF against B.1.1.7. Finally, using a separate intra-host mathematical model of viral kinetics, we demonstrate that a 0.6 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve 50% VEINF, which suggests that human challenge studies with a relatively low number of infected participants could be employed to estimate all three vaccine efficacy metrics.

Vaccine Development: From Laboratory to Policy.

Vaccines are one of the greatest public health achievements, protecting children and adults against numerous infectious diseases; however, the complex, rigorous process of vaccine development is unknown to many. A candidate vaccine undergoes extensive evaluation of safety and efficacy to meet licensure requirements before recommendations for use become policy. This time-consuming process involves an intricate collaboration among academia, public and private organizations, and federal agencies to ensure that safety is prioritized in every step. Vaccine safety continues to be monitored after licensure through a robust system. Yet, vaccine hesitancy remains a major challenge, especially now with the coronavirus disease 2019 (COVID-19) pandemic and concerns about the speed with which candidate vaccines are being developed. This article reviews the vaccine development process and the systems in place to ensure safety and effectiveness. A better understanding of these topics is necessary to address concerns and improve public acceptance of all vaccines, particularly COVID-19 vaccines. [Pediatr Ann. 2020;49(12):e509-e515.].

Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach.

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.

Potential impact of introducing vaccines against COVID-19 under supply and uptake constraints in France: A modelling study.

BACKGROUND: The accelerated vaccine development in response to the COVID-19 pandemic should lead to a vaccine being available early 2021, albeit in limited supply and possibly without full vaccine acceptance. We assessed the short-term impact of a COVID-19 immunization program with varying constraints on population health and non-pharmaceutical interventions (NPIs) needs. METHODS: A SARS-CoV-2 transmission model was calibrated to French epidemiological data. We defined several vaccine implementation scenarios starting in January 2021 based on timing of discontinuation of NPIs, supply and uptake constraints, and their relaxation. We assessed the number of COVID-19 hospitalizations averted, the need for and number of days with NPIs in place over the 2021-2022 period. RESULTS: An immunisation program under constraints could reduce the burden of COVID-19 hospitalizations by 9-40% if the vaccine prevents against infections. Relaxation of constraints not only reduces further COVID-19 hospitalizations (30-39% incremental reduction), it also allows for NPIs to be discontinued post-2021 (0 days with NPIs in 2022 versus 11 to 125 days for vaccination programs under constraints and 327 in the absence of vaccination). CONCLUSION: For 2021, COVID-19 control is expected to rely on a combination of NPIs and the outcome of early immunisation programs. The ability to overcome supply and uptake constraints will help prevent the need for further NPIs post-2021. As the programs expand, efficiency assessments will be needed to ensure optimisation of control policies post-emergency use.