Vaccination with soluble headless hemagglutinin protects mice from challenge with divergent influenza viruses

Vaccine. 2015 Jun 26;33(29):3314-21. doi: 10.1016/j.vaccine.2015.05.038. Epub 2015 May 28.


Current influenza virus vaccines provide solid protection from infection with viruses that are well matched with the vaccine strains. However, they do not protect efficiently against drifted or shifted strains. We developed an antigen based on the conserved stalk domain of the influenza virus hemagglutinin and tested its efficacy as a vaccine in a mouse virus challenge model. Although the antigen lacked the correct conformation of the native stalk domain and was not recognized by a panel of neutralizing stalk-reactive antibodies, it did induce considerable protection against H1N1, H5N1 and H6N1 challenge strains. Protection was enhanced when mice had pre-existing immunity against the stalk domain. Since pre-existing immunity is also present in the human population, we hypothesize that a similar antigen could show efficacy in humans as well.

Keywords: HA stalk; Headless hemagglutinin; Heterosubtypic immunity; Influenza virus; Universal influenza virus vaccine.

Publication types

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

MeSH terms

  • Animals
  • Cross Protection*
  • Disease Models, Animal
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / administration & dosage
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Influenza A virus / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections
  • Treatment Outcome
  • Vaccination / methods*


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines