An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies

Laura VanBlargan; John Errico; Peter Halfmann; Seth Zost; James Crowe; Lisa Purcell; Yoshihiro Kawaoka; Davide Corti; Daved Fremont; Michael Diamond

doi:10.21203/rs.3.rs-1175516/v1

An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies

Res Sq [Preprint]. 2021 Dec 27:rs.3.rs-1175516. doi: 10.21203/rs.3.rs-1175516/v1.

Authors

Laura VanBlargan¹, John Errico², Peter Halfmann³, Seth Zost⁴, James Crowe⁵, Lisa Purcell⁶, Yoshihiro Kawaoka⁷, Davide Corti⁸, Daved Fremont⁹, Michael Diamond¹⁰

Affiliations

¹ Department of Medicine, Washington University School of Medicine.
² Department of Pathology & Immunology, Washington University School of Medicine.
³ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
⁴ Vanderbilt Vaccine Center, Vanderbilt University Medical Center; Department of Pediatrics Vanderbilt University Medical Center.
⁵ Vanderbilt Vaccine Center, Vanderbilt University Medical Center; Department of Pediatrics Vanderbilt University Medical Center; Department of Pathology, and Microbiology and Immunology, Vanderbilt University Medical Center.
⁶ Vir Biotechnology.
⁷ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo; The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo.
⁸ Humabs BioMed SA, a subsidiary of Vir Biotechnology.
⁹ Department of Pathology & Immunology, Washington University School of Medicine; Department of Molecular Microbiology, Washington University School of Medicine; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine.
¹⁰ Department of Medicine and Department of Pathology & Immunology and Department of Molecular Microbiology, Washington University School of Medicine; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine.

Abstract

The emergence of the highly-transmissible B.1.1.529 Omicron variant of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is concerning for antibody countermeasure efficacy because of the number of mutations in the spike protein. Here, we tested a panel of anti-receptor binding domain monoclonal antibodies (mAbs) corresponding to those in clinical use by Vir Biotechnology (S309, the parent mAb of VIR-7831 [Sotrovimab]), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59) for their ability to neutralize an infectious B.1.1.529 Omicron isolate. Several mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost neutralizing activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (COV2-2196 and COV2-2130 combination, ~12-fold decrease) or minimally affected (S309). Our results suggest that several, but not all, of the antibodies in clinical use may lose efficacy against the B.1.1.529 Omicron variant.

Publication types

Preprint

Abstract

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