Tags

Type your tag names separated by a space and hit enter

Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies.
bioRxiv. 2020 May 29B

Abstract

Neutralizing antibody responses to coronaviruses focus on the trimeric spike, with most against the receptor-binding domain (RBD). Here we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their degree of focus on RBD epitopes, recognition of SARS-CoV, MERS-CoV, and mild coronaviruses, and how avidity effects contributed to increased binding/neutralization of IgGs over Fabs. Electron microscopy reconstructions of polyclonal plasma Fab-spike complexes showed recognition of both S1A and RBD epitopes. A 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-S complex revealed an epitope that blocks ACE2 receptor-binding on "up" RBDs. Modeling suggested that IgGs targeting these sites have different potentials for inter-spike crosslinking on viruses and would not be greatly affected by identified SARS-CoV-2 spike mutations. These 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 10065, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.Hospital Program Direction, The Rockefeller University, New York, NY 10065, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

Pub Type(s)

Preprint

Language

eng

PubMed ID

32577645

Citation

Barnes, Christopher O., et al. "Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies." BioRxiv : the Preprint Server for Biology, 2020.
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. bioRxiv. 2020.
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., Cetrulo Lorenzi, J. C., Finkin, S., Hagglof, 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. BioRxiv : the Preprint Server for Biology. https://doi.org/10.1101/2020.05.28.121533
Barnes CO, et al. Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. bioRxiv. 2020 May 29; PubMed PMID: 32577645.
* 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 - Cetrulo Lorenzi,Julio C, AU - Finkin,Shlomo, AU - Hagglof,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 - 2020/05/29/ PY - 2020/6/25/entrez PY - 2020/6/25/pubmed PY - 2020/6/25/medline KW - COVID-19 KW - Coronavirus KW - ELISA KW - Fab KW - IgG KW - MERS-CoV KW - SARS-CoV KW - SARS-CoV-2 KW - convalescent plasma KW - electron microscopy JF - bioRxiv : the preprint server for biology JO - bioRxiv N2 - Neutralizing antibody responses to coronaviruses focus on the trimeric spike, with most against the receptor-binding domain (RBD). Here we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their degree of focus on RBD epitopes, recognition of SARS-CoV, MERS-CoV, and mild coronaviruses, and how avidity effects contributed to increased binding/neutralization of IgGs over Fabs. Electron microscopy reconstructions of polyclonal plasma Fab-spike complexes showed recognition of both S1A and RBD epitopes. A 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-S complex revealed an epitope that blocks ACE2 receptor-binding on "up" RBDs. Modeling suggested that IgGs targeting these sites have different potentials for inter-spike crosslinking on viruses and would not be greatly affected by identified SARS-CoV-2 spike mutations. These 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. UR - https://www.unboundmedicine.com/medline/citation/32577645/Structures_of_human_antibodies_bound_to_SARS_CoV_2_spike_reveal_common_epitopes_and_recurrent_features_of_antibodies_ L2 - https://doi.org/10.1101/2020.05.28.121533 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.