Journal
CELL
Volume 182, Issue 1, Pages 73-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.05.025
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Funding
- Beijing Advanced Innovation Center for Genomics (ICG) at Peking University
- Fundamental Research Funds for the Central Universities [A20ZX00846]
- Beijing Municipal Commission of Science and Technology [Z201100005420018]
- National Mega projects of China for Major Infectious Diseases [2017ZX10304402]
- National Key Research and Development Project of China [2016YFD0500304]
- CAMS initiative for Innovative Medicine of China [2016-12M-2-006]
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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 angstrom 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 CDR3(H) 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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