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

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

  • Nat Commun. 2022 Jul 2;13(1):3824. doi: 10.1038/s41467-022-31615-7.
James Brett Case 1,  Samantha Mackin 1 2,  John M Errico 2,  Zhenlu Chong 1,  Emily A Madden 1,  Bradley Whitener 1,  Barbara Guarino 3,  Michael A Schmid 3,  Kim Rosenthal 4,  Kuishu Ren 4,  Ha V Dang 5,  Gyorgy Snell 5,  Ana Jung 2,  Lindsay Droit 2,  Scott A Handley 2,  Peter J Halfmann 6,  Yoshihiro Kawaoka 6 7 8,  James E Crowe Jr 9 10 11,  Daved H Fremont 2 12 13,  Herbert W Virgin 2 5 14,  Yueh-Ming Loo 4,  Mark T Esser 4,  Lisa A Purcell 5,  Davide Corti 3,  Michael S Diamond 15 16 17 18 19
Affiliations

Affiliations

  • 1 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • 2 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • 3 Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
  • 4 Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • 5 Vir Biotechnology, San Francisco, CA, USA.
  • 6 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • 7 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 8 The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
  • 9 Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 10 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 11 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 12 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  • 13 Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
  • 14 University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 15 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. mdiamond@wustl.edu.
  • 16 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA. mdiamond@wustl.edu.
  • 17 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. mdiamond@wustl.edu.
  • 18 Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA. mdiamond@wustl.edu.
  • 19 Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, Saint Louis, MO, USA. mdiamond@wustl.edu.
PMID: 35780162 DOI: 10.1038/s41467-022-31615-7
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.

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