Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

Elisabetta Cameroni, John E. Bowen, Laura E. Rosen, Christian Saliba, Samantha K. Zepeda, Katja Culap, Dora Pinto, Laura A. VanBlargan, Anna Marco, Julia Iulio, Fabrizia Zatta, Hannah Kaiser, Julia Noack, Nisar Farhat, Nadine Czudnochowski, Colin Havenar-Daughton, Kaitlin R. Sprouse, Josh R. Dillen, Abigail E. Powell, Alex Chen, Cyrus Maher, Li Yin, David Sun, Leah Soriaga, Jessica Bassi, Chiara Silacci-Fregni, Claes Gustafsson, Nicholas M. Franko, Jenni Logue, Najeeha Talat Iqbal, Ignacio Mazzitelli, Jorge Geffner, Renata Grifantini, Helen Chu, Andrea Gori, Agostino Riva, Olivier Giannini, Alessandro Ceschi, Paolo Ferrari, Pietro E. Cippà, Alessandra Franzetti-Pellanda, Christian Garzoni, Peter J. Halfmann, Yoshihiro Kawaoka, Christy Hebner, Lisa A. Purcell, Luca Piccoli, Matteo Samuele Pizzuto, Alexandra C. Walls, Michael S. Diamond, Amalio Telenti, Herbert W. Virgin, Antonio Lanzavecchia, Gyorgy Snell (), David Veesler () and Davide Corti ()
Additional contact information
Elisabetta Cameroni: Humabs Biomed SA, a subsidiary of Vir Biotechnology
John E. Bowen: University of Washington
Laura E. Rosen: Vir Biotechnology
Christian Saliba: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Samantha K. Zepeda: University of Washington
Katja Culap: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Dora Pinto: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Laura A. VanBlargan: Washington University of School of Medicine
Anna Marco: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Julia Iulio: Vir Biotechnology
Fabrizia Zatta: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Hannah Kaiser: Vir Biotechnology
Julia Noack: Vir Biotechnology
Nisar Farhat: Vir Biotechnology
Nadine Czudnochowski: Vir Biotechnology
Colin Havenar-Daughton: Vir Biotechnology
Kaitlin R. Sprouse: University of Washington
Josh R. Dillen: Vir Biotechnology
Abigail E. Powell: Vir Biotechnology
Alex Chen: Vir Biotechnology
Cyrus Maher: Vir Biotechnology
Li Yin: Vir Biotechnology
David Sun: Vir Biotechnology
Leah Soriaga: Vir Biotechnology
Jessica Bassi: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Chiara Silacci-Fregni: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Claes Gustafsson: ATUM
Nicholas M. Franko: University of Washington
Jenni Logue: University of Washington
Najeeha Talat Iqbal: Aga Khan University
Ignacio Mazzitelli: Universidad de Buenos Aires
Jorge Geffner: Universidad de Buenos Aires
Renata Grifantini: National Institute of Molecular Genetics
Helen Chu: University of Washington
Andrea Gori: Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico
Agostino Riva: Università di Milano
Olivier Giannini: Università della Svizzera italiana
Alessandro Ceschi: Università della Svizzera italiana
Paolo Ferrari: Università della Svizzera italiana
Pietro E. Cippà: Ente Ospedaliero Cantonale
Alessandra Franzetti-Pellanda: Clinica Luganese Moncucco
Christian Garzoni: Clinica Luganese Moncucco
Peter J. Halfmann: University of Wisconsin–Madison
Yoshihiro Kawaoka: University of Wisconsin–Madison
Christy Hebner: Vir Biotechnology
Lisa A. Purcell: Vir Biotechnology
Luca Piccoli: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Matteo Samuele Pizzuto: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Alexandra C. Walls: University of Washington
Michael S. Diamond: Washington University of School of Medicine
Amalio Telenti: Vir Biotechnology
Herbert W. Virgin: Vir Biotechnology
Antonio Lanzavecchia: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Gyorgy Snell: Vir Biotechnology
David Veesler: University of Washington
Davide Corti: Humabs Biomed SA, a subsidiary of Vir Biotechnology

Nature, 2022, vol. 602, issue 7898, 664-670

Abstract: Abstract The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody-based therapeutics. Here we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions in neutralizing activity were observed against Omicron compared to the ancestral pseudovirus in plasma from convalescent individuals and from individuals who had been vaccinated against SARS-CoV-2, but this loss was less pronounced after a third dose of vaccine. Most monoclonal antibodies that are directed against the receptor-binding motif lost in vitro neutralizing activity against Omicron, with only 3 out of 29 monoclonal antibodies retaining unaltered potency, including the ACE2-mimicking S2K146 antibody1. Furthermore, a fraction of broadly neutralizing sarbecovirus monoclonal antibodies neutralized Omicron through recognition of antigenic sites outside the receptor-binding motif, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major antigenic shift in SARS-CoV-2. Broadly neutralizing monoclonal antibodies that recognize RBD epitopes that are conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.

Date: 2022
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DOI: 10.1038/s41586-021-04386-2

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