Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects

Cell Rep. 2021 Jul 13;36(2):109353. doi: 10.1016/j.celrep.2021.109353. Epub 2021 Jun 22.


SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

Keywords: B.1.351; CV3-25; NTD; RBD; S2 subunit; SARS-CoV-1; SARS-CoV-2; monoclonal antibodies; neutralization.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / immunology
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology
  • Binding Sites
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • Cell Line
  • Cross Reactions
  • Epitopes / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Neutralization Tests
  • Protein Binding / immunology
  • Protein Domains
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2