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Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies.
Barnes, Christopher O; West, Anthony P; Huey-Tubman, Kathryn E; Hoffmann, Magnus A G; Sharaf, Naima G; Hoffman, Pauline R; Koranda, Nicholas; Gristick, Harry B; Gaebler, Christian; Muecksch, Frauke; Lorenzi, Julio C Cetrulo; Finkin, Shlomo; Hägglöf, Thomas; Hurley, Arlene; Millard, Katrina G; Weisblum, Yiska; Schmidt, Fabian; Hatziioannou, Theodora; Bieniasz, Paul D; Caskey, Marina; Robbiani, Davide F; Nussenzweig, Michel C; Bjorkman, Pamela J.
Afiliação
  • Barnes CO; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • West AP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Huey-Tubman KE; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Hoffmann MAG; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Sharaf NG; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Hoffman PR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Koranda N; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Gristick HB; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Gaebler C; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Muecksch F; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
  • Lorenzi JCC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Finkin S; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Hägglöf T; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Hurley A; Hospital Program Direction, The Rockefeller University, New York, NY, USA.
  • Millard KG; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Weisblum Y; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
  • Schmidt F; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
  • Hatziioannou T; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
  • Bieniasz PD; Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Caskey M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Robbiani DF; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: nussen@mail.rockefeller.edu.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. Electronic address: bjorkman@caltech.edu.
Cell ; 182(4): 828-842.e16, 2020 08 20.
Article em En | MEDLINE | ID: mdl-32645326
ABSTRACT
Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Imunoglobulina G / Fragmentos Fab das Imunoglobulinas / Infecções por Coronavirus / Anticorpos Neutralizantes / Glicoproteína da Espícula de Coronavírus / Betacoronavirus Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Imunoglobulina G / Fragmentos Fab das Imunoglobulinas / Infecções por Coronavirus / Anticorpos Neutralizantes / Glicoproteína da Espícula de Coronavírus / Betacoronavirus Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article