Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection

Cell Rep. 2020 Jul 21;32(3):107918. doi: 10.1016/j.celrep.2020.107918. Epub 2020 Jul 3.

Abstract

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.

Keywords: COVID-19; RBD; SARS-CoV-2; coronavirus; cross-neutralizing antibody; epitope; human antibodies; infection; neutralizing antibodies; spike protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology
  • Betacoronavirus / immunology*
  • COVID-19
  • Coronavirus Infections / therapy
  • Epitope Mapping
  • Epitopes / immunology
  • Humans
  • Immunologic Memory / immunology
  • Neutralization Tests
  • Pandemics
  • Pneumonia, Viral / therapy
  • Protein Domains / immunology
  • Receptors, Virus / immunology*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus