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      Evidence of leaky protection following COVID-19 vaccination and SARS-CoV-2 infection in an incarcerated population

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          Abstract

          Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent (“leaky”) protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25–0.54]; 0.57 [0.42–0.78]; 0.24 [0.15–0.39]; respectively) and with cellblock exposures (0.61 [0.49–0.75]; 0.69 [0.58–0.83]; 0.41 [0.31–0.55]; respectively) but not with cell exposures (0.89 [0.58–1.35]; 0.96 [0.64–1.46]; 0.80 [0.46–1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.

          Abstract

          Measuring an individual’s level of exposure to COVID-19 is challenging, and it is therefore unclear whether high exposure may impact immunity. Here, the authors investigate this question using data from a correctional facility in Connecticut, USA, by comparing rates of infection in people who share cells, cellblocks, and with no known exposure.

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

              Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. Methods In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. Results A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. Conclusions The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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                Author and article information

                Contributors
                Margaret.Lind@yale.edu
                Albert.Ko@yale.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                19 August 2023
                19 August 2023
                2023
                : 14
                : 5055
                Affiliations
                [1 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Epidemiology of Microbial Diseases, , Yale School of Public Health, ; New Haven, CT USA
                [2 ]Connecticut Department of Correction, Wethersfield, CT USA
                [3 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Pediatrics, Yale School of Medicine, ; New Haven, CT USA
                [4 ]GRID grid.47100.32, ISNI 0000000419368710, Yale Institute for Global Health, Yale School of Public Health, ; New Haven, CT USA
                [5 ]GRID grid.267313.2, ISNI 0000 0000 9482 7121, UT Southwestern, School of Public Health, ; Dallas, TX USA
                [6 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Internal Medicine, , Yale School of Medicine, ; New Haven, CT USA
                [7 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Laboratory Medicine, , Yale University School of Medicine, ; New Haven, CT USA
                [8 ]GRID grid.168010.e, ISNI 0000000419368956, Division of Infectious Diseases and Geographic Medicine, , Stanford University, ; Stanford, CA USA
                [9 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Department of Biostatistics, College of Public Health & Health Professions, , University of Florida, ; Gainesville, FL USA
                [10 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Department of Biology, , University of Florida, ; Gainesville, FL USA
                [11 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Emerging Pathogens Institute, , University of Florida, ; Gainesville, FL USA
                [12 ]GRID grid.418068.3, ISNI 0000 0001 0723 0931, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, ; Salvador, BA Brazil
                Author information
                http://orcid.org/0000-0002-1572-4074
                http://orcid.org/0000-0002-8631-0020
                http://orcid.org/0000-0002-2048-4028
                http://orcid.org/0000-0002-5967-251X
                http://orcid.org/0000-0003-2327-3557
                http://orcid.org/0000-0002-9437-1907
                http://orcid.org/0000-0001-9023-2339
                Article
                40750
                10.1038/s41467-023-40750-8
                10439918
                37598213
                89e3ebb4-8016-4bb8-8e97-959535b95698
                © Springer Nature Limited 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 March 2023
                : 7 August 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/100004824, State of Connecticut Department of Public Health (Connecticut Department of Public Health);
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                © Springer Nature Limited 2023

                Uncategorized
                viral infection,epidemiology,sars-cov-2
                Uncategorized
                viral infection, epidemiology, sars-cov-2

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