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      Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera

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          Abstract

          Rapidly spreading variants of SARS-CoV-2 that have arisen in the United Kingdom and South Africa share the spike N501Y substitution, which is of particular concern because it is located in the viral receptor binding site for cell entry and increases binding to the receptor (angiotensin converting enzyme 2). We generated isogenic N501 and Y501 SARS-CoV-2. Sera of 20 participants in a previously reported trial of the mRNA-based COVID-19 vaccine BNT162b2 had equivalent neutralizing titers to the N501 and Y501 viruses.

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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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            Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy

            Modeling SARS-CoV-2 in mice Among the research tools necessary to develop medical interventions to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, high on the list are informative animal models with which to study viral pathogenesis. Gu et al. developed a mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia. Adaptation of this viral strain in the mouse appeared to be dependent on a critical amino acid change, Asn501 to Tyr (N501Y), within the receptor-binding domain of the viral spike protein. The new mouse model was used to study neutralizing antibodies and a vaccine candidate against the virus. Science, this issue p. 1603
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              Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa

              Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.
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                Author and article information

                Journal
                bioRxiv
                BIORXIV
                bioRxiv
                Cold Spring Harbor Laboratory
                07 January 2021
                : 2021.01.07.425740
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston TX, U.S.A.
                [2 ]Pfizer, 401 N Middletown Rd., Pearl River, NY 10960, U.S.A.
                [3 ]Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston TX, U.S.A.
                [4 ]Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA
                [5 ]Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, U.S.A.
                [6 ]Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, U.S.A.
                [7 ]Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, U.S.A.
                Author notes

                Author contributions

                Conceptualization, X.P., V.D.M., S.W., P.-Y.S.; Methodology, X.P., J.Z., C.R.F.G., H.X., P.-Y.S; Investigation, X.P., J.Z., C.R.F.G., H.X., K.A.S., D.C., P.R.D., P.-Y.S; Resources, M.C., D.C., P.R.D., P.-Y.S; Data Curation, X.P., J.Z., C.R.F.G., P.-Y.S; Writing-Original Draft, X.P., P.-Y.S; Writing-Review & Editing, X.P., P.R.D., P.-Y.S.; Supervision, X.P., M.C., D.C., P.R.D., P.-Y.S.; Funding Acquisition P.-Y.S.

                [# ]Correspondence: P.R.D. ( Philip.Dormitzer@ 123456pfizer.com ) or P.-Y.S. ( peshi@ 123456UTMB.edu )
                Article
                10.1101/2021.01.07.425740
                7805448
                33442691
                36ff5e9f-afa1-48bc-b1d5-3f0cb5b7c230

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

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