Selected article for: "cryo em and spike trimer"
Author: Cao, Yunlong; Su, Bin; Guo, Xianghua; Sun, Wenjie; Deng, Yongqiang; Bao, Linlin; Zhu, Qinyu; Zhang, Xu; Zheng, Yinghui; Geng, Chenyang; Chai, Xiaoran; He, Runsheng; Li, Xiaofeng; Lv, Qi; Zhu, Hua; Deng, Wei; Xu, Yanfeng; Wang, Yanjun; Qiao, Luxin; Tan, Yafang; Song, Liyang; Wang, Guopeng; Du, Xiaoxia; Gao, Ning; Liu, Jiangning; Xiao, Junyu; Su, Xiao-dong; Du, Zongmin; Feng, Yingmei; Qin, Chuan; Qin, Chengfeng; Jin, Ronghua; Xie, X. Sunney
Title: Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells
  • Cord-id: 721ofhsv
  • Document date: 2020_5_18
    • ID: 721ofhsv
    Snippet: Summary 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 ng/mL and 15 ng/mL against pseudotyped and authentic SARS-CoV-2
    Document: Summary 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 ng/mL 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 3.8Å 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.

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