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Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies.
Cell. 2020 08 20; 182(4):828-842.e16.Cell

Abstract

Neutralizing 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.

Authors+Show Affiliations

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Hospital Program Direction, The Rockefeller University, New York, NY, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: nussen@mail.rockefeller.edu.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. Electronic address: bjorkman@caltech.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32645326

Citation

Barnes, Christopher O., et al. "Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies." Cell, vol. 182, no. 4, 2020, pp. 828-842.e16.
Barnes CO, West AP, Huey-Tubman KE, et al. Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Cell. 2020;182(4):828-842.e16.
Barnes, C. O., West, A. P., Huey-Tubman, K. E., Hoffmann, M. A. G., Sharaf, N. G., Hoffman, P. R., Koranda, N., Gristick, H. B., Gaebler, C., Muecksch, F., Lorenzi, J. C. C., Finkin, S., Hägglöf, T., Hurley, A., Millard, K. G., Weisblum, Y., Schmidt, F., Hatziioannou, T., Bieniasz, P. D., ... Bjorkman, P. J. (2020). Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Cell, 182(4), 828-e16. https://doi.org/10.1016/j.cell.2020.06.025
Barnes CO, et al. Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Cell. 2020 08 20;182(4):828-842.e16. PubMed PMID: 32645326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. AU - Barnes,Christopher O, AU - West,Anthony P,Jr AU - Huey-Tubman,Kathryn E, AU - Hoffmann,Magnus A G, AU - Sharaf,Naima G, AU - Hoffman,Pauline R, AU - Koranda,Nicholas, AU - Gristick,Harry B, AU - Gaebler,Christian, AU - Muecksch,Frauke, AU - Lorenzi,Julio C Cetrulo, AU - Finkin,Shlomo, AU - Hägglöf,Thomas, AU - Hurley,Arlene, AU - Millard,Katrina G, AU - Weisblum,Yiska, AU - Schmidt,Fabian, AU - Hatziioannou,Theodora, AU - Bieniasz,Paul D, AU - Caskey,Marina, AU - Robbiani,Davide F, AU - Nussenzweig,Michel C, AU - Bjorkman,Pamela J, Y1 - 2020/06/24/ PY - 2020/05/11/received PY - 2020/05/27/revised PY - 2020/06/15/accepted PY - 2020/7/10/pubmed PY - 2020/8/28/medline PY - 2020/7/10/entrez KW - COVID-19 KW - ELISA KW - Fab KW - IgG KW - MERS-CoV KW - SARS-CoV KW - SARS-CoV-2 KW - convalescent plasma KW - coronavirus KW - electron microscopy SP - 828 EP - 842.e16 JF - Cell JO - Cell VL - 182 IS - 4 N2 - Neutralizing 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. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/32645326/Structures_of_Human_Antibodies_Bound_to_SARS_CoV_2_Spike_Reveal_Common_Epitopes_and_Recurrent_Features_of_Antibodies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)30757-1 DB - PRIME DP - Unbound Medicine ER -