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

[tetano]

Cell Discov


. 2021 Jul 20;7(1):53.
doi: 10.1038/s41421-021-00292-z.
Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants


Jianhui Nie ^{# 1} , Jingshu Xie ^{# 2} , Shuo Liu ^{# 1} , Jiajing Wu ^{# 1} , Chuan Liu ^{# 3} , Jianhui Li ² , Yacui Liu ² , Meiyu Wang ¹ , Huizhen Zhao ² , Yabo Zhang ² , Jiawei Yao ² , Lei Chen ² , Yuelei Shen ² , Yi Yang ⁴ , Hong-Wei Wang ⁵ , Youchun Wang ⁶ , Weijin Huang ⁷



Affiliations

• PMID: 34285195
• DOI: 10.1038/s41421-021-00292-z

Abstract

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.