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

Abstract

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.

• Authors: Hejun Liu, Meng Yuan, Deli Huang, Sandhya Bangaru, Fangzhu Zhao, Chang-Chun D Lee, Linghang Peng, Shawn Barman, Xueyong Zhu, David Nemazee, Dennis R Burton, Marit J van Gils, Rogier W Sanders, Hans-Christian Kornau, S Momsen Reincke, Harald Prüss, Jakob Kreye, Nicholas C Wu, Andrew B Ward, Ian A Wilson
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 29 Issue 5 Pg. 806-818.e6 (05 12 2021) ISSN: 1934-6069 [Electronic] United States
• PMID: 33894127 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Spike Glycoprotein, Coronavirus
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (metabolism)
• Antibodies, Neutralizing (chemistry, immunology)
• Antibodies, Viral (chemistry, immunology)
• COVID-19 (prevention & control)
• Cross Reactions
• Humans
• Severe acute respiratory syndrome-related coronavirus (immunology)
• SARS-CoV-2 (immunology)
• Severe Acute Respiratory Syndrome (prevention & control)
• Spike Glycoprotein, Coronavirus (metabolism)