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         description:Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccine against SARS-CoV-21–4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small—but significant—margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5–8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid a potential loss of clinical efficacy. The Moderna (mRNA-1273) and Pfizer–BioNTech (BNT162b2) vaccines elicit anti-RBD antibodies similar to those elicited through natural infection with SARS-CoV-2, but their potent neutralizing activity was reduced or abolished by new viral variants of concern.
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      headline:mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
      description:Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccine against SARS-CoV-21–4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small—but significant—margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5–8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid a potential loss of clinical efficacy. The Moderna (mRNA-1273) and Pfizer–BioNTech (BNT162b2) vaccines elicit anti-RBD antibodies similar to those elicited through natural infection with SARS-CoV-2, but their potent neutralizing activity was reduced or abolished by new viral variants of concern.
      datePublished:2021-02-10T00:00:00Z
      dateModified:2021-02-10T00:00:00Z
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         Antimicrobial responses
         SARS-CoV-2
         Science
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      affiliation:
            name:The Rockefeller University
            address:
               name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
               type:PostalAddress
            type:Organization
            name:The Rockefeller University
            address:
               name:Howard Hughes Medical Institute, The Rockefeller University, New York, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Retrovirology, The Rockefeller University, New York, USA
      name:Laboratory of Retrovirology, The Rockefeller University, New York, USA
      name:Laboratory of Retrovirology, The Rockefeller University, New York, USA
      name:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, USA
      name:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, USA
      name:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, USA
      name:Hospital Program Direction, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Retrovirology, The Rockefeller University, New York, USA
      name:Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, USA
      name:Pediatric Translational Research Branch and Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, USA
      name:Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, USA
      name:The NIH Regulome Project, National Institutes of Health, Bethesda, USA
      name:Laboratory of Retrovirology, The Rockefeller University, New York, USA
      name:Laboratory of Retrovirology, The Rockefeller University, New York, USA
      name:Howard Hughes Medical Institute, The Rockefeller University, New York, USA
      name:Laboratory of Molecular Immunology, The Rockefeller University, New York, USA
      name:Howard Hughes Medical Institute, The Rockefeller University, New York, USA

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