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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. C. Lorenzi, Shlomo Finkin, Thomas Hägglöf, Arlene Hurley, Katrina G. Millard, Yiska Weisblum, Fabian Schmidt, Théodora Hatziioannou, Paul D. Bieniasz, Marina Caskey, Davide F. Robbiani, Michel C. Nussenzweig, Pamela J. Björkman

2020Cell928 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

EpitopePolyclonal antibodiesAvidityAntibodyBiologyVirologyMonoclonal antibodyNeutralizationEpitope mappingLinear epitopeSpike ProteinSpike (software development)Immunoglobulin GPolyclonal B cell responseCoronavirusImmunologyCoronavirus disease 2019 (COVID-19)B cellB-cell receptorMedicineManagementEconomicsDiseasePathologyInfectious disease (medical specialty)SARS-CoV-2 and COVID-19 ResearchMonoclonal and Polyclonal Antibodies ResearchAnimal Virus Infections Studies