4.8 Article

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

Journal

NATURE MEDICINE
Volume 28, Issue 3, Pages 490-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01678-y

Keywords

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Funding

  1. National Institues of Health [R01 AI157155, U01 AI151810, 75N93021C00014, HHSN272201700060C, 75N93019C00062, 75N93019C00051]
  2. Defense Advanced Research Project Agency [HR0011-18-2-0001]
  3. Japan Program for Infectious Diseases Research and Infrastructure from the Japan Agency for Medical Research and Development [JP21wm0125002]
  4. Dolly Parton COVID-19 Research Fund at Vanderbilt University Medical Center

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The emergence of the B.1.1.529 Omicron variant raises concerns about the efficacy of antibody countermeasures. This study shows that some of the antibodies currently in clinical use may lose their ability to neutralize the Omicron variant.
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. In this study, 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), Eli 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, similar to 12-fold decrease) or minimally affected (S309). Our results suggest that several, but not all, of the antibodies in clinical use might lose efficacy against the B.1.1.529 Omicron variant.

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