tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 [/SUP], Jingshu Xie[SUP] #[/SUP][SUP] 2 [/SUP], Shuo Liu[SUP] #[/SUP][SUP] 1 [/SUP], Jiajing Wu[SUP] #[/SUP][SUP] 1 [/SUP], Chuan Liu[SUP] #[/SUP][SUP] 3 [/SUP], Jianhui Li[SUP] 2 [/SUP], Yacui Liu[SUP] 2 [/SUP], Meiyu Wang[SUP] 1 [/SUP], Huizhen Zhao[SUP] 2 [/SUP], Yabo Zhang[SUP] 2 [/SUP], Jiawei Yao[SUP] 2 [/SUP], Lei Chen[SUP] 2 [/SUP], Yuelei Shen[SUP] 2 [/SUP], Yi Yang[SUP] 4 [/SUP], Hong-Wei Wang[SUP] 5 [/SUP], Youchun Wang[SUP] 6 [/SUP], Weijin Huang[SUP] 7 [/SUP]
Affiliations
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.
. 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[SUP] #[/SUP][SUP] 1 [/SUP], Jingshu Xie[SUP] #[/SUP][SUP] 2 [/SUP], Shuo Liu[SUP] #[/SUP][SUP] 1 [/SUP], Jiajing Wu[SUP] #[/SUP][SUP] 1 [/SUP], Chuan Liu[SUP] #[/SUP][SUP] 3 [/SUP], Jianhui Li[SUP] 2 [/SUP], Yacui Liu[SUP] 2 [/SUP], Meiyu Wang[SUP] 1 [/SUP], Huizhen Zhao[SUP] 2 [/SUP], Yabo Zhang[SUP] 2 [/SUP], Jiawei Yao[SUP] 2 [/SUP], Lei Chen[SUP] 2 [/SUP], Yuelei Shen[SUP] 2 [/SUP], Yi Yang[SUP] 4 [/SUP], Hong-Wei Wang[SUP] 5 [/SUP], Youchun Wang[SUP] 6 [/SUP], Weijin Huang[SUP] 7 [/SUP]
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.