In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains

Rita E. Chen, Emma S. Winkler, James Brett Case, Ishmael D. Aziati, Traci L. Bricker, Astha Joshi, Tamarand L. Darling, Baoling Ying, John M. Errico, Swathi Shrihari, Laura A. VanBlargan, Xuping Xie, Pavlo Gilchuk, Seth J. Zost, Lindsay Droit, Zhuoming Liu, Spencer Stumpf, David Wang, Scott A. Handley, W. Blaine Stine, Pei-Yong Shi, Meredith E. Davis-Gardner, Mehul S. Suthar, Miguel Garcia Knight, Raul Andino, Charles Y. Chiu, Ali H. Ellebedy, Daved H. Fremont, Sean P. J. Whelan, James E. Crowe, Lisa Purcell, Davide Corti, Adrianus C. M. Boon and Michael S. Diamond ()
Additional contact information
Rita E. Chen: Washington University School of Medicine
Emma S. Winkler: Washington University School of Medicine
James Brett Case: Washington University School of Medicine
Ishmael D. Aziati: Washington University School of Medicine
Traci L. Bricker: Washington University School of Medicine
Astha Joshi: Washington University School of Medicine
Tamarand L. Darling: Washington University School of Medicine
Baoling Ying: Washington University School of Medicine
John M. Errico: Washington University School of Medicine
Swathi Shrihari: Washington University School of Medicine
Laura A. VanBlargan: Washington University School of Medicine
Xuping Xie: University of Texas Medical Branch
Pavlo Gilchuk: Vanderbilt University Medical Center
Seth J. Zost: Vanderbilt University Medical Center
Lindsay Droit: Washington University School of Medicine
Zhuoming Liu: Washington University School of Medicine
Spencer Stumpf: Washington University School of Medicine
David Wang: Washington University School of Medicine
Scott A. Handley: Washington University School of Medicine
W. Blaine Stine: AbbVie Bioresearch Center
Pei-Yong Shi: University of Texas Medical Branch
Meredith E. Davis-Gardner: Emory University School of Medicine
Mehul S. Suthar: Emory University School of Medicine
Miguel Garcia Knight: University of California San Francisco
Raul Andino: University of California San Francisco
Charles Y. Chiu: University of California San Francisco
Ali H. Ellebedy: Washington University School of Medicine
Daved H. Fremont: Washington University School of Medicine
Sean P. J. Whelan: Washington University School of Medicine
James E. Crowe: Vanderbilt University Medical Center
Lisa Purcell: Vir Biotechnology
Davide Corti: a subsidiary of Vir Biotechnology
Adrianus C. M. Boon: Washington University School of Medicine
Michael S. Diamond: Washington University School of Medicine

Nature, 2021, vol. 596, issue 7870, 103-108

Abstract: Abstract Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21–3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many—but not all—of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.

Date: 2021
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DOI: 10.1038/s41586-021-03720-y

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