C. Barnes, A. West, Kathryn E Huey-Tubman, Magnus A. G. Hoffmann, N. G. Sharaf, Pauline R Hoffman, Nicholas Koranda, H. Gristick, C. Gaebler, F. Muecksch, J. C. Lorenzi, Shlomo Finkin, Thomas Hägglöf, A. Hurley, Katrina G Millard, Y. Weisblum, F. Schmidt, T. Hatziioannou, P. Bieniasz, M. Caskey, D. Robbiani, M. Nussenzweig, P. Bjorkman
Cell, 2020
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 3.4Å 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.
Cited by 184 publications.
Field of study: Biology