PT - JOURNAL ARTICLE AU - Lihong Liu AU - Sho Iketani AU - Yicheng Guo AU - Jasper F-W. Chan AU - Maple Wang AU - Liyuan Liu AU - Yang Luo AU - Hin Chu AU - Yiming Huang AU - Manoj S. Nair AU - Jian Yu AU - Kenn K-H. Chik AU - Terrence T-T. Yuen AU - Chaemin Yoon AU - Kelvin K-W. To AU - Honglin Chen AU - Michael T. Yin AU - Magdalena E. Sobieszczyk AU - Yaoxing Huang AU - Harris H. Wang AU - Zizhang Sheng AU - Kwok-Yung Yuen AU - David D. Ho TI - Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2 AID - 10.1101/2021.12.14.472719 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.12.14.472719 4099 - http://biorxiv.org/content/early/2021/12/15/2021.12.14.472719.short 4100 - http://biorxiv.org/content/early/2021/12/15/2021.12.14.472719.full AB - The Omicron (B.1.1.529) variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 18 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.Competing Interest StatementL.L., S.I., M.S.N., J.Y., Y.H., and D.D.H. are inventors on patent applications on some of the antibodies described in this manuscript.