Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site

Nat Commun. 2022 Dec 21;13(1):7864. doi: 10.1038/s41467-022-35586-7.

Abstract

Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal* / chemistry
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / metabolism
  • Catalytic Domain / immunology
  • Catalytic Domain / physiology
  • Glycosylation
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Humans
  • Influenza A Virus, H3N2 Subtype* / immunology
  • Influenza A Virus, H3N2 Subtype* / metabolism
  • Influenza A virus
  • Influenza, Human / immunology
  • Influenza, Human / metabolism
  • Neuraminidase* / chemistry
  • Neuraminidase* / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Neuraminidase