TY - JOUR
T1 - A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge
AU - Zhou, Biao
AU - Zhou, Runhong
AU - Tang, Bingjie
AU - Chan, Jasper Fuk Woo
AU - Luo, Mengxiao
AU - Peng, Qiaoli
AU - Yuan, Shuofeng
AU - Liu, Hang
AU - Mok, Bobo Wing Yee
AU - Chen, Bohao
AU - Wang, Pui
AU - Poon, Vincent Kwok Man
AU - Chu, Hin
AU - Chan, Chris Chung Sing
AU - Tsang, Jessica Oi Ling
AU - Chan, Chris Chun Yiu
AU - Au, Ka Kit
AU - Man, Hiu On
AU - Lu, Lu
AU - To, Kelvin Kai Wang
AU - Chen, Honglin
AU - Yuen, Kwok Yung
AU - Dang, Shangyu
AU - Chen, Zhiwei
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-31259-7
DO - 10.1038/s41467-022-31259-7
M3 - Article
C2 - 35739114
AN - SCOPUS:85132560512
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3589
ER -