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,
Harry B. Gristick,
Julio C Cetrulo Lorenzi,
Katrina G Millard,
Paul D. Bieniasz,
Davide F Robbiani,
Michel C. Nussenzweig,
Posted 29 May 2020
bioRxiv DOI: 10.1101/2020.05.28.121533 (published DOI: 10.1016/j.cell.2020.06.025)
Posted 29 May 2020
Neutralizing antibody responses to coronaviruses focus on the trimeric spike, with most against the receptor-binding domain (RBD). Here we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their degree of focus on RBD epitopes, recognition of SARS-CoV, MERS-CoV, and mild coronaviruses, and how avidity effects contributed to increased binding/neutralization of IgGs over Fabs. Electron microscopy reconstructions of polyclonal plasma Fab-spike complexes showed recognition of both S1A and RBD epitopes. In addition, a 3.4 Å cryo-EM structure of a neutralizing monoclonal Fab-S complex revealed an epitope that blocks ACE2 receptor-binding on up RBDs. Modeling suggested that IgGs targeting these sites have different potentials for inter-spike crosslinking on viruses and would not be greatly affected by identified SARS-CoV-2 spike mutations. These 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. ### Competing Interest Statement The authors have declared no competing interest.
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