title: Vaccination with soluble headless hemagglutinin protects mice from challenge with divergent influenza viruses.
abstract: 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.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Teddy John
authors.initials: TJ
authors.lastname: Wohlbold
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Faculty of Life Sciences, University of Vienna, Vienna, Austria.
authors.forename: Raffael
authors.initials: R
authors.lastname: Nachbagauer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Margine
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Gene S
authors.initials: GS
authors.lastname: Tan
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ariana
authors.initials: A
authors.lastname: Hirsh
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: florian.krammer@mssm.edu.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
mesh_terms: D000818:Animals; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: HA stalk; Headless hemagglutinin; Heterosubtypic immunity; Influenza virus; Universal influenza virus vaccine