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

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

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

Cell Host Microbe. 2021 May 12;29(5):806-818.e6. doi: 10.1016/j.chom.2021.04.005. Epub 2021 Apr 15.

Authors

Hejun Liu¹, Meng Yuan¹, Deli Huang², Sandhya Bangaru¹, Fangzhu Zhao², Chang-Chun D Lee¹, Linghang Peng², Shawn Barman², Xueyong Zhu¹, David Nemazee², Dennis R Burton³, Marit J van Gils⁴, Rogier W Sanders⁵, Hans-Christian Kornau⁶, S Momsen Reincke⁷, Harald Prüss⁷, Jakob Kreye⁸, Nicholas C Wu⁹, Andrew B Ward¹, Ian A Wilson¹⁰

Affiliations

¹ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
² Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
⁴ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
⁶ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁷ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Helmholtz Innovation Lab BaoBab, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁸ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Helmholtz Innovation Lab BaoBab, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁹ Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
¹⁰ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu.

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.

Keywords: 3D structure; COVID-19; SARS-CoV-2; antibody cocktail; antibody-antigen interaction; coronavirus; cross-neutralizing antibody; crystallography; synergy.

Publication types

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

MeSH terms

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding