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      The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines

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          ABSTRACT

          The emergence of several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against the alpha variant (B.1.1.7), while some vaccines have reduced efficacy and effectiveness against symptomatic disease caused by the beta variant (B.1.351) and the delta variant (B.1.617.2); however, effectiveness against severe disease and hospitalization caused by delta remains high. Although data on the effectiveness of the primary regimen against omicron (B.1.1.529) are limited, booster programs using mRNA vaccines have been shown to restore protection against infection and symptomatic disease (regardless of the vaccine used for the primary regimen) and maintain high effectiveness against hospitalization. However, effectiveness against infection and symptomatic disease wanes with time after the booster dose. Studies have demonstrated reductions of varying magnitude in neutralizing activity of vaccine-elicited antibodies against a range of SARS-CoV-2 variants, with the omicron variant in particular exhibiting partial immune escape. However, evidence suggests that T-cell responses are preserved across vaccine platforms, regardless of variant of concern. Nevertheless, various mitigation strategies are under investigation to address the potential for reduced efficacy or effectiveness against current and future SARS-CoV-2 variants, including modification of vaccines for certain variants (including omicron), multivalent vaccine formulations, and different delivery mechanisms.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

            Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.
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              Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

              Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                mBio
                mBio
                mbio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                30 March 2022
                Mar-Apr 2022
                30 March 2022
                : 13
                : 2
                : e02979-21
                Affiliations
                [a ] School of Human Sciences, London Metropolitan Universitygrid.23231.31, and National Heart and Lung Institute, Imperial College London, London, United Kingdom
                [b ] Louisiana State University Health, Shreveport, Louisiana, USA
                [c ] Icahn School of Medicine at Mount Sinai, New York, New York, USA
                [d ] Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa
                [e ] MRC Antibody Immunity Research Unit, School of Pathology, The University of the Witwatersrand, Johannesburg, South Africa
                [f ] Institute of Virology, Hannover Medical Schoolgrid.10423.34, , Hannover, Germany
                [g ] Cluster of Excellence 2155 RESIST, Hannover, Germany
                [h ] German Centre for Infection Research, Hannover-Braunschweig Site, Germany
                [i ] BioNTech, Mainz, Germany
                Albert Einstein College of Medicine
                Author notes

                The authors declare a conflict of interest. GRM, TFS, BL, and PLM have no conflicts of interest to report. ÖT and US are management board members and employees at BioNTech SE (Mainz, Germany). JK has a grant from the Rockefeller Foundation to increase equity and representativeness in SARS-CoV-2 sequencing, has a role on an NIH grant to carry out SARS-CoV-2 sequencing and detection of viral variants, served on a BioNTech advisory panel, and holds stock in BioNTech and Pfizer, who manufacture COVID-19 vaccines. AM and SP are employees at BioNTech SE. AM, ÖT, and US are inventors on patents and patent applications related to RNA technology and COVID-19 vaccines. AM, ÖT, and US have securities from BioNTech SE.

                Author information
                https://orcid.org/0000-0002-1278-1743
                https://orcid.org/0000-0001-8422-7656
                https://orcid.org/0000-0003-0760-1709
                https://orcid.org/0000-0001-8719-4028
                https://orcid.org/0000-0001-8792-5345
                https://orcid.org/0000-0003-4561-2273
                https://orcid.org/0000-0003-0363-1564
                https://orcid.org/0000-0003-1244-6264
                Article
                02979-21 mbio.02979-21
                10.1128/mbio.02979-21
                9040821
                35352979
                c167af88-ae4f-4f9f-86a1-b79d882f09cf
                Copyright © 2022 McLean et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 8 February 2022
                Page count
                supplementary-material: 3, Figures: 1, Tables: 1, Equations: 0, References: 187, Pages: 24, Words: 18725
                Funding
                Funded by: BioNtech;
                Award ID: N/A
                Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient :
                Categories
                Minireview
                vaccines, Vaccines
                Custom metadata
                March/April 2022

                Life sciences
                sars-cov-2,covid-19,vaccines,mutation,variant
                Life sciences
                sars-cov-2, covid-19, vaccines, mutation, variant

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