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. Epub 2020 May 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / isolation & purification*
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / isolation & purification*
  • Antibodies, Neutralizing / metabolism
  • B-Lymphocytes / immunology*
  • COVID-19
  • Convalescence
  • Coronavirus Infections / immunology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mice
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Sequence Analysis, RNA
  • Single-Cell Analysis*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism
  • VDJ Exons

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2