An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

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...

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Published in:Science translational medicine 2022-05, Vol.14 (646), p.eabn6859-eabn6859
Main Authors: Liu, Lihong, Iketani, Sho, Guo, Yicheng, Reddem, Eswar R, Casner, Ryan G, 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
Format: Article
Language:English
Subjects:
Antibodies
Antibodies, Viral
BASIC BIOLOGICAL SCIENCES
Coronavirus
Coronaviruses
COVID-19
Epitopes
Humans
Immunoglobulin Isotypes
Monoclonal antibodies
Pandemics
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus
STM r-articles
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Summary: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.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.abn6859