Publications
Science translational medicineApr 2022 |
eabn6859
DOI:
10.1126/scitranslmed.abn6859

An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

Liu, Lihong; Iketani, Sho; Guo, Yicheng; Casner, Ryan G; Reddem, Eswar R; Nair, Manoj S; Yu, Jian; Chan, Jasper F-W; Wang, Maple; Cerutti, Gabriele; Li, Zhiteng; Morano, Nicholas C; Castagna, Candace D; Corredor, Laura; Chu, Hin; Yuan, Shuofeng; Poon, Vincent Kwok-Man; Chan, Chris Chun-Sing; Chen, Zhiwei; Luo, Yang; Cunningham, Marcus; Chavez, Alejandro; Yin, Michael T; Perlin, David S; Tsuji, Moriya; Yuen, Kwok-Yung; Kwong, Peter D; Sheng, Zizhang; Huang, Yaoxing; Shapiro, Lawrence; Ho, David D
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Abstract
The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well-conserved among sarbecoviruses, but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.
Product Used
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