Human neutralizing antibodies elicited by SARS-CoV-2 infection

被引：1097

作者：

Ju, Bin ^{[1
,2
]}

Zhang, Qi ^{[3
,4
,5
]}

Ge, Jiwan ^{[6
]}

Wang, Ruoke ^{[3
,4
,5
]}

Sun, Jing ^{[7
]}

Ge, Xiangyang ^{[1
]}

Yu, Jiazhen ^{[1
]}

Shan, Sisi ^{[3
,4
,5
]}

Zhou, Bing ^{[1
]}

Song, Shuo ^{[1
]}

Tang, Xian ^{[1
]}

Yu, Jinfang ^{[6
]}

Lan, Jun ^{[6
]}

Yuan, Jing ^{[8
]}

Wang, Haiyan ^{[1
]}

Zhao, Juanjuan ^{[1
,2
]}

Zhang, Shuye ^{[9
,10
]}

Wang, Youchun ^{[11
]}

Shi, Xuanling ^{[3
,4
,5
]}

Liu, Lei ^{[1
,2
]}

Zhao, Jincun ^{[7
]}

Wang, Xinquan ^{[6
]}

Zhang, Zheng ^{[1
,2
]}

Zhang, Linqi ^{[3
,4
,5
]}

机构：

[1] Shenzhen Third Peoples Hosp, Inst Hepatol, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China

[2] Southern Univ Sci & Technol, Sch Med, Affiliated Hosp 2, Shenzhen, Peoples R China

[3] Tsinghua Univ, Comprehens AIDS Res Ctr, Ctr Global Hlth & Infect Dis, Beijing, Peoples R China

[4] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Med, Beijing, Peoples R China

[5] Tsinghua Univ, Vanke Sch Publ Hlth, Beijing, Peoples R China

[6] Tsinghua Univ, Collaborat Innovat Ctr Biotherapy,Sch Life Sci, Beijing Frontier Res Ctr Biol Struct,Minist Educ, Beijing Adv Innovat Ctr Struct Biol,Key Lab Prot, Beijing, Peoples R China

[7] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou, Peoples R China

[8] Shenzhen Third Peoples Hosp, Dept Infect Dis, Shenzhen, Peoples R China

[9] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China

[10] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[11] Natl Inst Food & Drug Control, Div HIV AIDS & Sex Transmitted Virus Vaccines, Beijing, Peoples R China

来源：

NATURE | 2020年 / 584卷 / 7819期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

SARS CORONAVIRUS; SPIKE PROTEIN; COV; VACCINE; BINDING;

D O I：

10.1038/s41586-020-2380-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention(1-3). The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)(2,4-6). Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2. In a study of antibodies isolated from patients infected with SARS-CoV-2, antibodies that potently neutralized the virus competed with angiotensin-converting enzyme 2 for binding to the receptor-binding domain of the viral spike protein, suggesting that antibodies that disrupt this interaction could be developed to treat SARS-CoV-2 infection.

引用

页码：115 / +

页数：18