Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2021.12.15.472828; this version posted December 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by 2 several therapeutic monoclonal antibodies 3 4 Laura A. VanBlargan1, John M. Errico2, Peter J. Halfmann3, Seth J. Zost4,5, James E. Crowe 5 Jr.4,5,6, Lisa A. Purcell7, Yoshihiro Kawaoka3,8,9, Davide Corti10, Daved H. Fremont2,11,12, and 6 Michael S. Diamond1,2,11,13,14 7 8 1 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA 9 2 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 10 USA 11 3 12 University of Wisconsin-Madison, Madison, WI, USA. 13 4 Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA 14 5 Department of Pediatrics Vanderbilt University Medical Center, Nashville, TN, USA 15 6 Department of Pathology, and Microbiology and Immunology, Vanderbilt University Medical Center, 16 Nashville, TN, USA 17 7 Vir Biotechnology, St Louis, MO, USA. 18 8 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, 19 University of Tokyo, 108-8639 Tokyo, Japan. 20 9 21 Research Institute, Tokyo 162-8655, Japan. 22 10 Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland. 23 11 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO. 24 12 Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. 25 Louis, MO. 26 13 27 Washington University School of Medicine, Saint Louis, MO. 28 14 29 Saint Louis, MO. 30 Corresponding author: Michael S. Diamond, M.D., Ph.D., mdiamond@wustl.edu Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.12.15.472828; this version posted December 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 31 ABSTRACT 32 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the 33 global COVID-19 pandemic resulting in millions of deaths worldwide. Despite the 34 development and deployment of highly effective antibody and vaccine countermeasures, 35 rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike 36 protein jeopardize their efficacy. Indeed, the recent emergence of the highly-transmissible 37 B.1.1.529 Omicron variant is especially concerning because of the number of mutations, 38 deletions, and insertions in the spike protein. Here, using a panel of anti-receptor binding 39 domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency..