Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations...

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Veröffentlicht in:Cell discovery 2021-07, Vol.7 (1), p.53-53, Article 53
Hauptverfasser: Nie, Jianhui, Xie, Jingshu, Liu, Shuo, Wu, Jiajing, Liu, Chuan, Li, Jianhui, Liu, Yacui, Wang, Meiyu, Zhao, Huizhen, Zhang, Yabo, Yao, Jiawei, Chen, Lei, Shen, Yuelei, Yang, Yi, Wang, Hong-Wei, Wang, Youchun, Huang, Weijin
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Sprache:eng
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Zusammenfassung:Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.
ISSN:2056-5968
2056-5968
DOI:10.1038/s41421-021-00292-z