Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2021.12.14.472719; this version posted December 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2 1 Lihong Liu1*, Sho Iketani1,2*, Yicheng Guo1*, Jasper F-W. Chan3, 4*, Maple Wang1*, Liyuan 2 Liu5*, Yang Luo1, Hin Chu3,4, Yiming Huang5, Manoj S. Nair1, Jian Yu1, Kenn K-H. Chik4, 3 Terrence T-T. Yuen3, Chaemin Yoon3, Kelvin K-W. To3,4, Honglin Chen3,4, Michael T. Yin1,6, 4 Magdalena E. Sobieszczyk1,6, Yaoxing Huang1, Harris H. Wang5, Zizhang Sheng1, 5 Kwok-Yung Yuen3,4, David D. Ho1,2,6^ 6 7 1 8 Surgeons, New York, NY 10032, USA 9 2 Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Department of Microbiology and Immunology, Columbia University Vagelos College of 10 Physicians and Surgeons, New York, NY 10032, USA 11 3 12 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 13 Pokfulam, Hong Kong Special Administrative Region, China 14 4 15 Hong Kong Special Administrative Region, China 16 5 17 Surgeons, New York, NY 10032, USA 18 6 19 of Physicians and Surgeons, New York, NY 10032, USA State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Department of Systems Biology, Columbia University Vagelos College of Physicians and Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College 20 21 * These authors contributed equally 22 ^ Address correspondence to David D. Ho (dh2994@cumc.columbia.edu, 212-304-6101, 701 W 23 168th St, 11th Floor, New York, NY 10032) 24 25 Word count: 3309 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.12.14.472719; this version posted December 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 26 Abstract 27 28 The Omicron (B.1.1.529) variant of SARS-CoV-2 was only recently detected in southern Africa, 29 but its subsequent spread has been extensive, both regionally and globally1. It is expected to 30 become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking 31 feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of 32 current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings 33 from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only 34 from convalescent patients, but also from individuals vaccinated with one of the four widely used 35 COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based 36 vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating 37 a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that 38 the activity of 18 of the 19 antibodies tested were either abolished or impaired, including ones 39 currently authorized or approved for use in patients. In addition, we also identified four new spike 40 mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance..