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Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2

Lihong Liu, View ORCID ProfileSho Iketani, Yicheng Guo, Jasper F-W. Chan, Maple Wang, Liyuan Liu, Yang Luo, Hin Chu, Yiming Huang, Manoj S. Nair, Jian Yu, Kenn K-H. Chik, Terrence T-T. Yuen, Chaemin Yoon, Kelvin K-W. To, Honglin Chen, Michael T. Yin, Magdalena E. Sobieszczyk, Yaoxing Huang, Harris H. Wang, View ORCID ProfileZizhang Sheng, Kwok-Yung Yuen, David D. Ho
doi: https://doi.org/10.1101/2021.12.14.472719
Lihong Liu
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Sho Iketani
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
2Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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  • ORCID record for Sho Iketani
Yicheng Guo
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Jasper F-W. Chan
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
4Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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Maple Wang
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Liyuan Liu
5Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Yang Luo
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Hin Chu
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
4Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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Yiming Huang
5Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Manoj S. Nair
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Jian Yu
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Kenn K-H. Chik
4Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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Terrence T-T. Yuen
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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Chaemin Yoon
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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Kelvin K-W. To
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
4Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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Honglin Chen
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
4Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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Michael T. Yin
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
6Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Magdalena E. Sobieszczyk
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
6Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Yaoxing Huang
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Harris H. Wang
5Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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Zizhang Sheng
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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  • ORCID record for Zizhang Sheng
Kwok-Yung Yuen
3State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
4Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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David D. Ho
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
2Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
6Division of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
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  • For correspondence: dh2994@cumc.columbia.edu
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Abstract

The Omicron (B.1.1.529) variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 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 (coronavirus disease 2019) 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 17 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 Statement

L.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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 21, 2021.
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Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2
Lihong Liu, Sho Iketani, Yicheng Guo, Jasper F-W. Chan, Maple Wang, Liyuan Liu, Yang Luo, Hin Chu, Yiming Huang, Manoj S. Nair, Jian Yu, Kenn K-H. Chik, Terrence T-T. Yuen, Chaemin Yoon, Kelvin K-W. To, Honglin Chen, Michael T. Yin, Magdalena E. Sobieszczyk, Yaoxing Huang, Harris H. Wang, Zizhang Sheng, Kwok-Yung Yuen, David D. Ho
bioRxiv 2021.12.14.472719; doi: https://doi.org/10.1101/2021.12.14.472719
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Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2
Lihong Liu, Sho Iketani, Yicheng Guo, Jasper F-W. Chan, Maple Wang, Liyuan Liu, Yang Luo, Hin Chu, Yiming Huang, Manoj S. Nair, Jian Yu, Kenn K-H. Chik, Terrence T-T. Yuen, Chaemin Yoon, Kelvin K-W. To, Honglin Chen, Michael T. Yin, Magdalena E. Sobieszczyk, Yaoxing Huang, Harris H. Wang, Zizhang Sheng, Kwok-Yung Yuen, David D. Ho
bioRxiv 2021.12.14.472719; doi: https://doi.org/10.1101/2021.12.14.472719

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