Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells

被引：984

作者：

Cao, Yunlong ^{[1
,2
]}

Su, Bin ^{[3
]}

Guo, Xianghua ^{[3
]}

Sun, Wenjie ^{[1
,2
]}

Deng, Yongqiang ^{[4
]}

Bao, Linlin ^{[5
,6
]}

Zhu, Qinyu ^{[7
,8
]}

Zhang, Xu ^{[9
]}

Zheng, Yinghui ^{[1
,2
]}

Geng, Chenyang ^{[1
,2
]}

Chai, Xiaoran ^{[1
,2
]}

He, Runsheng ^{[1
,2
]}

Li, Xiaofeng ^{[4
]}

Lv, Qi ^{[5
,6
]}

Zhu, Hua ^{[5
,6
]}

Deng, Wei ^{[5
,6
]}

Xu, Yanfeng ^{[5
,6
]}

Wang, Yanjun ^{[3
]}

Qiao, Luxin ^{[3
]}

Tan, Yafang ^{[4
]}

Song, Liyang ^{[1
,2
,7
]}

Wang, Guopeng ^{[7
]}

Du, Xiaoxia ^{[1
,2
,7
]}

Gao, Ning ^{[8
,10
]}

Liu, Jiangning ^{[5
,6
]}

Xiao, Junyu ^{[7
,8
]}

Su, Xiao-dong ^{[1
,2
,7
]}

Du, Zongmin ^{[4
]}

Feng, Yingmei ^{[3
]}

Qin, Chuan ^{[5
,6
]}

Qin, Chengfeng ^{[4
]}

Jin, Ronghua ^{[3
]}

Xie, X. Sunney ^{[1
,2
,8
,11
]}

机构：

[1] Peking Univ, Beijing Adv Innovat Ctr Genom ICG, Beijing 100871, Peoples R China

[2] Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Beijing 100871, Peoples R China

[3] Capital Med Univ, Beijing Youan Hosp, Beijing 100069, Peoples R China

[4] Acad Mil Med Sci, Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China

[5] Chinese Acad Med Sci, Chinese Minist Hlth, Inst Lab Anim Sci,Beijing Key Lab Anim Models Eme, Key Lab Human Dis Comparat Med, Beijing, Peoples R China

[6] Peking Union Med Coll, Comparat Med Ctr, Beijing, Peoples R China

[7] Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing, Peoples R China

[8] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci CLS, Beijing 100871, Peoples R China

[9] Singl Beijing DanXu Pharmaceut, Beijing 102206, Peoples R China

[10] Peking Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing, Peoples R China

[11] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China

来源：

CELL | 2020年 / 182卷 / 01期

关键词：

HUMAN MONOCLONAL-ANTIBODIES; SPIKE PROTEIN; VIRUS; PREDICTION; IMMUNOGLOBULIN; INFECTION; DOMAIN; BROAD; DATABASE; BINDING;

D O I：

10.1016/j.cell.2020.05.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1(+) clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 angstrom cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3(H) structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.

引用

页码：73 / +

页数：28

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