Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Christopher O. Barnes, Anthony P. West, Kathryn E. Huey-Tubman, Magnus A.G. Hoffmann, Naima G. Sharaf, Pauline R. Hoffman, Nicholas Koranda, Harry B. Gristick, Christian Gaebler, Frauke Muecksch, Julio C.Cetrulo Lorenzi, Shlomo Finkin, Thomas Hägglöf, Arlene Hurley, Katrina G. Millard, Yiska Weisblum, Fabian Schmidt, Theodora Hatziioannou, Paul D. Bieniasz, Marina CaskeyDavide F. Robbiani, Michel C. Nussenzweig*, Pamela J. Bjorkman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

492 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)828-842.e16
JournalCell
Volume182
Issue number4
DOIs
StatePublished - Aug 20 2020

Keywords

  • convalescent plasma
  • coronavirus
  • COVID-19
  • electron microscopy
  • ELISA
  • Fab
  • IgG
  • MERS-CoV
  • SARS-CoV
  • SARS-CoV-2

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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