• Cell · Aug 2020

    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 Caskey, Davide F Robbiani, Michel C Nussenzweig, and Pamela J Bjorkman.
    • Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
    • Cell. 2020 Aug 20; 182 (4): 828-842.e16.

    AbstractNeutralizing 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.Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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