Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants
Autor: | Hong-Wei Wang, Huizhen Zhao, Yuelei Shen, Youchun Wang, Jiajing Wu, Weijin Huang, Jingshu Xie, Jianhui Nie, Lei Chen, Jiawei Yao, Meiyu Wang, Shuo Liu, Yabo Zhang, Jianhui Li, Liu Yacui, Chuan Liu, Yi Yang |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Pattern recognition receptors
0301 basic medicine biology Coronavirus disease 2019 (COVID-19) QH573-671 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mutant Rational design Cell Biology Biochemistry Virology Article Epitope 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Epitope mapping Cryoelectron microscopy Genetics biology.protein Antibody Neutralizing antibody Cytology Molecular Biology 030217 neurology & neurosurgery |
Zdroj: | Cell Discovery, Vol 7, Iss 1, Pp 1-11 (2021) Cell Discovery |
ISSN: | 2056-5968 |
Popis: | 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. |
Databáze: | OpenAIRE |
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