Highlights

  • 8,558 IgG1+ antigen-binding clonotypes were identified by high-throughput scRNA/VDJ-seq
  • 14 potent SARS-CoV-2 neutralizing antibodies were found from 60 convalescent patients
  • BD-368-2 showed high therapeutic and prophylactic efficacy in SARS-CoV-2-infected mice
  • Neutralizing antibodies can be directly selected based on predicted CDR3H structures

May 17, 2020

DOI:https://doi.org/10.1016/j.cell.2020.05.025

Reprinted for educational purposes and social benefit, not for profit.

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 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.

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