TY - JOUR
T1 - An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies
AU - VanBlargan, Laura A.
AU - Errico, John M.
AU - Halfmann, Peter J.
AU - Zost, Seth J.
AU - Crowe, James E.
AU - Purcell, Lisa A.
AU - Kawaoka, Yoshihiro
AU - Corti, Davide
AU - Fremont, Daved H.
AU - Diamond, Michael S.
N1 - Funding Information:
M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics and Merck Sharp & Dohme, is on the Scientific Advisory Board of Meissa Vaccines and is the founder of IDBiologics. The Crowe laboratory has received sponsored research agreements from Takeda Vaccines, AstraZeneca and IDBiologics. Vanderbilt University has applied for patents related to two antibodies discussed in this paper. L.A.P. and D.C. are employees of Vir Biotechnology and may hold stock shares in Vir Biotechnology. L.A.P. is a former employee and shareholder in Regeneron Pharmaceuticals. The remaining authors declare no competing interests.
Funding Information:
This study was supported by grants and contracts from the National Institues of Health (R01 AI157155 (to M.S.D. and J.E.C), U01 AI151810 (to M.S.D.), 75N93021C00014 (to Y.K.), HHSN272201700060C (to D.H.F.), 75N93019C00062 (D.H.F. and M.S.D.), and 75N93019C00051 (to M.S.D.)); the Defense Advanced Research Project Agency (HR0011-18-2-0001 (to J.E.C. and M.S.D)); the Japan Program for Infectious Diseases Research and Infrastructure (JP21wm0125002) from the Japan Agency for Medical Research and Development (to Y.K.); and the Dolly Parton COVID-19 Research Fund at Vanderbilt University Medical Center (to J.E.C.). We thank R. Nargi, R. Carnahan, T. Tan and L. Schimanski for assistance and generosity with mAb generation and purification and S. A. Turner from the Center for Pathogen Evolution at the University of Cambridge for evaluating B.1.1.529 sequences. AZD7442 (AZD8895 and AZD1061) was supplied by AstraZeneca under a material transfer agreement.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/3
Y1 - 2022/3
N2 - 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, ~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.
AB - 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, ~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.
UR - http://www.scopus.com/inward/record.url?scp=85123161100&partnerID=8YFLogxK
U2 - 10.1038/s41591-021-01678-y
DO - 10.1038/s41591-021-01678-y
M3 - Article
C2 - 35046573
AN - SCOPUS:85123161100
SN - 1078-8956
VL - 28
SP - 490
EP - 495
JO - Nature medicine
JF - Nature medicine
IS - 3
ER -