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

Abstract：

: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 Å 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 CDR3H 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.

journal_name

Cell

journal_title

Cell

authors

Cao Y,Su B,Guo X,Sun W,Deng Y,Bao L,Zhu Q,Zhang X,Zheng Y,Geng C,Chai X,He R,Li X,Lv Q,Zhu H,Deng W,Xu Y,Wang Y,Qiao L,Tan Y,Song L,Wang G,Du X,Gao N,Liu J,Xiao J,Su XD,Du Z,Feng Y,Qin C,Qin C

doi

10.1016/j.cell.2020.05.025

subject

Has Abstract

pub_date

2020-07-09 00:00:00

pages

73-84.e16

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(20)30620-6

journal_volume

182

pub_type

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