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

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

  • Cell. 2020 Jul 9;182(1):73-84.e16. doi: 10.1016/j.cell.2020.05.025.
Yunlong Cao 1,  Bin Su 2,  Xianghua Guo 2,  Wenjie Sun 1,  Yongqiang Deng 3,  Linlin Bao 4,  Qinyu Zhu 5,  Xu Zhang 6,  Yinghui Zheng 1,  Chenyang Geng 1,  Xiaoran Chai 1,  Runsheng He 1,  Xiaofeng Li 3,  Qi Lv 4,  Hua Zhu 4,  Wei Deng 4,  Yanfeng Xu 4,  Yanjun Wang 2,  Luxin Qiao 2,  Yafang Tan 3,  Liyang Song 7,  Guopeng Wang 8,  Xiaoxia Du 7,  Ning Gao 9,  Jiangning Liu 4,  Junyu Xiao 5,  Xiao-Dong Su 7,  Zongmin Du 3,  Yingmei Feng 2,  Chuan Qin 10,  Chengfeng Qin 11,  Ronghua Jin 12,  X Sunney Xie 13
Affiliations

Affiliations

  • 1 Beijing Advanced Innovation Center for Genomics (ICG) & Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China.
  • 2 Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
  • 3 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • 4 Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.
  • 5 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences (CLS), Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 6 Singlomics (Beijing DanXu Pharmaceuticals), Beijing 102206, China.
  • 7 Beijing Advanced Innovation Center for Genomics (ICG) & Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
  • 8 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
  • 9 Peking-Tsinghua Center for Life Sciences (CLS), Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.
  • 10 Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China. Electronic address: qinchuan@pumc.edu.cn.
  • 11 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China. Electronic address: qincf@bmi.ac.cn.
  • 12 Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. Electronic address: ronghuajin_youan@126.com.
  • 13 Beijing Advanced Innovation Center for Genomics (ICG) & Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences (CLS), Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: sunneyxie@pku.edu.cn.
PMID: 32425270 DOI: 10.1016/j.cell.2020.05.025
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.

Keywords

B cell; CDR3; COVID-19; SARS-CoV-2; convalescent patient; neutralizing antibody; single-cell sequencing.

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