Structural basis for broad neutralization of human antibody against Omicron sublineages and evasion by XBB variant

J Virol. 2023 Nov 30;97(11):e0113723. doi: 10.1128/jvi.01137-23. Epub 2023 Oct 19.

Abstract

The ongoing COVID-19 pandemic has been characterized by the emergence of new SARS-CoV-2 variants including the highly transmissible Omicron XBB sublineages, which have shown significant resistance to neutralizing antibodies (nAbs). This resistance has led to decreased vaccine effectiveness and therefore result in breakthrough infections and reinfections, which continuously threaten public health. To date, almost all available therapeutic nAbs, including those authorized under Emergency Use Authorization nAbs that were previously clinically useful against early strains, have recently been found to be ineffective against newly emerging variants. In this study, we provide a comprehensive structural basis about how the Class 3 nAbs, including 1G11 in this study and noted LY-CoV1404, are evaded by the newly emerged SARS-CoV-2 variants.

Keywords: SARS-CoV-2; broad neutralization; cryo-EM; immune evasion; neutralizing antibody.

MeSH terms

  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral
  • Breakthrough Infections
  • COVID-19* / immunology
  • COVID-19* / virology
  • Humans
  • Pandemics*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral

Supplementary concepts

  • SARS-CoV-2 variants