A potent, broadly neutralizing human monoclonal antibody that efficiently protects hACE2-transgenic mice from infection with the Wuhan, BA.5, and XBB.1.5 SARS-CoV-2 variants

Front Immunol. 2024 Jul 19:15:1442160. doi: 10.3389/fimmu.2024.1442160. eCollection 2024.

Abstract

The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro, iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape.

Keywords: COVID-19; Omicron; SARS-CoV-1; iC1 antibody; in vivo protection.

MeSH terms

  • Angiotensin-Converting Enzyme 2* / genetics
  • Angiotensin-Converting Enzyme 2* / immunology
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Animals
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / immunology
  • Betacoronavirus / genetics
  • Betacoronavirus / immunology
  • Broadly Neutralizing Antibodies / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • COVID-19* / virology
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / virology
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic*
  • Pandemics / prevention & control
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / prevention & control
  • Pneumonia, Viral / virology
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology

Substances

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

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement No 075-15-2021-1086, contract No RF—193021X0015, 15.ИП.21.0015).