Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity

Liu, Hejun; Wu, Nicholas C.; Yuan, Meng; Bangaru, Sandhya; Torres, Jonathan L.; Caniels, Tom G.; van Schooten, Jelle; Zhu, Xueyong; Lee, Chang-Chun D.; Brouwer, Philip J. M.; van Gils, Marit J.; Sanders, Rogier W.; Ward, Andrew B.; Wilson, Ian A.

doi:10.1016/j.immuni.2020.10.023

Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity

Journal Article · Tue Nov 24 23:00:00 EST 2020 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2020.10.023· OSTI ID:1816211

Liu, Hejun ^[1]; Wu, Nicholas C. ^[2]; Yuan, Meng ^[2]; Bangaru, Sandhya ^[2]; Torres, Jonathan L. ^[2]; Caniels, Tom G. ^[3]; van Schooten, Jelle ^[3]; Zhu, Xueyong ^[2]; Lee, Chang-Chun D. ^[2]; Brouwer, Philip J. M. ^[3]; van Gils, Marit J. ^[3]; Sanders, Rogier W. ^[4]; Ward, Andrew B. ^[5]; Wilson, Ian A. ^[6]

The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology; OSTI
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology
Univ. of Amsterdam (Netherlands). Amsterdam UMC. Dept. of Medical Microbiology
Univ. of Amsterdam (Netherlands). Amsterdam UMC. Dept. of Medical Microbiology; Cornell Univ., Ithaca, NY (United States). Weill Medical College. Dept. of Microbiology and Immunology
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology; The Scripps Research Inst., La Jolla, CA (United States). IAVI Neutralizing Antibody Center; The Scripps Research Inst., La Jolla, CA (United States). Consortium for HIV/AIDS Vaccine Development (CHAVD)
The Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology. IAVI Neutralizing Antibody Center. Consortium for HIV/AIDS Vaccine Development (CHAVD). The Skaggs Institute for Chemical Biology

Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here, we determined a crystal structure of the COVA1-16 antibody fragment (Fab) with the SARS-CoV-2 receptor-binding domain (RBD) and negative-stain electron microscopy reconstructions with the spike glycoprotein trimer to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long complementarity-determining region (CDR) H3, and competes with the angiotensin-converting enzyme 2 (ACE2) receptor because of steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with the structural and functional rationale for epitope conservation, provide insights for development of more universal SARS-like coronavirus vaccines and therapies.

View Accepted Manuscript (DOE)

Research Organization:: The Scripps Research Inst., La Jolla, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1816211

Journal Information:: Immunity, Journal Name: Immunity Journal Issue: 6 Vol. 53; ISSN 1074-7613

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

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Additional file 2 of Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants Yi, Chunyan; Sun, Xiaoyu; Lin, Yixiao figshare https://doi.org/10.6084/m9.figshare.16815702	dataset	January 2021
Additional file 3 of Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants Yi, Chunyan; Sun, Xiaoyu; Lin, Yixiao figshare https://doi.org/10.6084/m9.figshare.16815705	dataset	January 2021
Additional file 4 of Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants Yi, Chunyan; Sun, Xiaoyu; Lin, Yixiao figshare https://doi.org/10.6084/m9.figshare.16815708	dataset	January 2021

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