Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies

• Published in: bioRxiv 2020-05
• Main Authors: Barnes, Christopher O, West, Jr, 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, Cetrulo Lorenzi, Julio C, Finkin, Shlomo, Hagglof, 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
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin-converting enzyme 2; Antibodies; Avidity; Coronaviridae; Coronaviruses; COVID-19; Electron microscopy; Epitopes; Fab; Severe acute respiratory syndrome coronavirus 2
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2020.05.28.121533

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 S1 and RBD epitopes. A 3.4Å 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 and similarity to a SARS-CoV antibody, providing criteria for evaluating vaccine-elicited antibodies.