A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge

Biao Zhou, Runhong Zhou, Bingjie Tang, Jasper Fuk-Woo Chan, Mengxiao Luo, Qiaoli Peng, Shuofeng Yuan, Hang Liu, Bobo Wing-Yee Mok, Bohao Chen, Pui Wang, Vincent Kwok-Man Poon, Hin Chu, Chris Chung-Sing Chan, Jessica Oi-Ling Tsang, Chris Chun-Yiu Chan, Ka-Kit Au, Hiu-On Man, Lu Lu, Kelvin Kai-Wang To, Honglin Chen, Kwok-Yung Yuen, Shangyu Dang () and Zhiwei Chen ()
Additional contact information
Biao Zhou: The University of Hong Kong
Runhong Zhou: The University of Hong Kong
Bingjie Tang: The Hong Kong University of Science and Technology
Jasper Fuk-Woo Chan: The University of Hong Kong
Mengxiao Luo: The University of Hong Kong
Qiaoli Peng: The University of Hong Kong
Shuofeng Yuan: The University of Hong Kong
Hang Liu: The Hong Kong University of Science and Technology
Bobo Wing-Yee Mok: The University of Hong Kong
Bohao Chen: The University of Hong Kong
Pui Wang: The University of Hong Kong
Vincent Kwok-Man Poon: The University of Hong Kong
Hin Chu: The University of Hong Kong
Chris Chung-Sing Chan: The University of Hong Kong
Jessica Oi-Ling Tsang: The University of Hong Kong
Chris Chun-Yiu Chan: The University of Hong Kong
Ka-Kit Au: The University of Hong Kong
Hiu-On Man: The University of Hong Kong
Lu Lu: The University of Hong Kong
Kelvin Kai-Wang To: The University of Hong Kong
Honglin Chen: The University of Hong Kong
Kwok-Yung Yuen: The University of Hong Kong
Shangyu Dang: The Hong Kong University of Science and Technology
Zhiwei Chen: The University of Hong Kong

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.

Date: 2022
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DOI: 10.1038/s41467-022-31259-7

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