Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

James Brett Case, Samantha Mackin, John M. Errico, Zhenlu Chong, Emily A. Madden, Bradley Whitener, Barbara Guarino, Michael A. Schmid, Kim Rosenthal, Kuishu Ren, Ha V. Dang, Gyorgy Snell, Ana Jung, Lindsay Droit, Scott A. Handley, Peter J. Halfmann, Yoshihiro Kawaoka, James E. Crowe, Daved H. Fremont, Herbert W. Virgin, Yueh-Ming Loo, Mark T. Esser, Lisa A. Purcell, Davide Corti and Michael S. Diamond ()
Additional contact information
James Brett Case: Washington University School of Medicine
Samantha Mackin: Washington University School of Medicine
John M. Errico: Washington University School of Medicine
Zhenlu Chong: Washington University School of Medicine
Emily A. Madden: Washington University School of Medicine
Bradley Whitener: Washington University School of Medicine
Barbara Guarino: a subsidiary of Vir Biotechnology
Michael A. Schmid: a subsidiary of Vir Biotechnology
Kim Rosenthal: BioPharmaceuticals R&D, AstraZeneca
Kuishu Ren: BioPharmaceuticals R&D, AstraZeneca
Ha V. Dang: Vir Biotechnology
Gyorgy Snell: Vir Biotechnology
Ana Jung: Washington University School of Medicine
Lindsay Droit: Washington University School of Medicine
Scott A. Handley: Washington University School of Medicine
Peter J. Halfmann: University of Wisconsin-Madison
Yoshihiro Kawaoka: University of Wisconsin-Madison
James E. Crowe: Vanderbilt University Medical Center
Daved H. Fremont: Washington University School of Medicine
Herbert W. Virgin: Washington University School of Medicine
Yueh-Ming Loo: BioPharmaceuticals R&D, AstraZeneca
Mark T. Esser: BioPharmaceuticals R&D, AstraZeneca
Lisa A. Purcell: Vir Biotechnology
Davide Corti: a subsidiary of Vir Biotechnology
Michael S. Diamond: Washington University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.

Date: 2022
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DOI: 10.1038/s41467-022-31615-7

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