A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction

Nat Commun. 2020 Aug 21;11(1):4198. doi: 10.1038/s41467-020-18058-8.

Abstract

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / metabolism
  • Betacoronavirus / immunology*
  • Chlorocebus aethiops
  • Cross Reactions
  • Epitopes
  • HEK293 Cells
  • Humans
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / metabolism
  • Immunoglobulin A, Secretory / immunology
  • Immunoglobulin A, Secretory / metabolism
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Models, Molecular
  • Mutation
  • Peptidyl-Dipeptidase A / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • SARS Virus / immunology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Vero Cells

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • Immunoglobulin A
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Supplementary concepts

  • severe acute respiratory syndrome coronavirus 2