Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus

Nat Commun. 2014 Apr 10;5:3614. doi: 10.1038/ncomms4614.

Abstract

Influenza viruses present a significant health challenge each year, as in the H3N2 epidemic of 2012-2013. Here we describe an antibody, F045-092, that possesses broadly neutralizing activity against the entire H3 subtype and accommodates the natural variation and additional glycosylation in all strains tested from 1963 to 2011. Crystal structures of F045-092 in complex with HAs from 1975 and 2011 H3N2 viruses reveal the structural basis for its neutralization breadth through insertion of its 23-residue HCDR3 into the receptor-binding site that involves striking receptor mimicry. F045-092 extends its recognition to divergent subtypes, including H1, H2 and H13, using the enhanced avidity of its IgG to overcome lower-affinity Fab binding, as observed with other antibodies that target the receptor-binding site. This unprecedented level of antibody cross-reactivity against the H3 subtype can potentially inform on development of a pan-H3 vaccine or small-molecule therapeutics.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / metabolism*
  • Antibodies, Viral / metabolism*
  • Binding Sites
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Influenza A Virus, H3N2 Subtype / metabolism*
  • Influenza A virus / metabolism

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus

Associated data

  • PDB/4O58
  • PDB/4O5I
  • PDB/4O5L
  • PDB/4O5N