A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Liu, Hejun; Yuan, Meng; Huang, Deli; Bangaru, Sandhya; Zhao, Fangzhu; Lee, Chang-Chun D.; Peng, Linghang; Barman, Shawn; Zhu, Xueyong; Nemazee, David; Burton, Dennis R.; van Gils, Marit J.; Sanders, Rogier W.; Kornau, Hans-Christian; Reincke, S. Momsen; Prüss, Harald; Kreye, Jakob; Wu, Nicholas C.; Ward, Andrew B.; Wilson, Ian A.

doi:10.1016/j.chom.2021.04.005

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Journal Article · Thu Apr 15 00:00:00 EDT 2021 · Cell Host & Microbe

DOI:https://doi.org/10.1016/j.chom.2021.04.005· OSTI ID:1810870

Liu, Hejun ^[1]; Yuan, Meng ^[1]; Huang, Deli ^[1]; Bangaru, Sandhya ^[1]; Zhao, Fangzhu ^[1]; Lee, Chang-Chun D. ^[1]; Peng, Linghang ^[1]; Barman, Shawn ^[1]; Zhu, Xueyong ^[1]; Nemazee, David ^[1]; Burton, Dennis R. ^[2]; van Gils, Marit J. ^[3]; Sanders, Rogier W. ^[4]; Kornau, Hans-Christian ^[5]; Reincke, S. Momsen ^[6]; Prüss, Harald ^[6]; Kreye, Jakob ^[6]; Wu, Nicholas C. ^[7]; Ward, Andrew B. ^[1]; Wilson, Ian A. ^[1]

The Scripps Research Inst., La Jolla, CA (United States)
The Scripps Research Inst., La Jolla, CA (United States); Ragon Institute of MGH, MIT and Harvard, Cambridge, MA (United States)
Univ. of Amsterdam (Netherlands)
Univ. of Amsterdam (Netherlands); Cornell Univ., Ithaca, NY (United States). Weill Medical College
German Center for Neurodegenerative Diseases (DZNE), Berlin (Germany); Charité – Universitätsmedizin Berlin (Germany)
German Center for Neurodegenerative Diseases (DZNE), Berlin (Germany); Helmholtz Innovation Lab BaoBab, Berlin (Germany); Charité – Universitätsmedizin Berlin (Germany)
Univ. of Illinois at Urbana-Champaign, IL (United States)

Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Bill and Melinda Gates Foundation; German Research Foundation (DFG); National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1810870

Alternate ID(s):: OSTI ID: 1812075

Journal Information:: Cell Host & Microbe, Journal Name: Cell Host & Microbe Journal Issue: 5 Vol. 29; ISSN 1931-3128

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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