Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer

J Virol. 2015 Jul;89(14):7417-20. doi: 10.1128/JVI.00808-15. Epub 2015 Apr 29.


We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA3-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA3-SS has increased thermostability compared to wild-type HA, and binding of head- and stem-targeted antibodies (Abs) is preserved; only minor structural changes are found in the vicinity of the additional disulfide. This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens.

Publication types

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

MeSH terms

  • Antibodies, Viral / immunology*
  • Antigens, Viral / chemistry*
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Disulfides*
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Orthomyxoviridae / genetics
  • Orthomyxoviridae / immunology*
  • Protein Binding
  • Protein Stability
  • Temperature


  • Antibodies, Viral
  • Antigens, Viral
  • Disulfides
  • Hemagglutinin Glycoproteins, Influenza Virus