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; Cetrulo Lorenzi, Julio C.; 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.

Summary Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal 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 3.4Ã… 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 that 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.