title: An H7N1 influenza virus vaccine induces broadly reactive antibody responses against H7N9 in humans.
abstract: Emerging H7N9 influenza virus infections in Asia have once more spurred the development of effective prepandemic H7 vaccines. However, many vaccines based on avian influenza viruses--including H7--are poorly immunogenic, as measured by traditional correlates of protection. Here we reevaluated sera from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses to divergent H7 strains, including H7N9, dissected the antibody response into head- and stalk-reactive antibodies, and tested the in vivo potency of these human sera in a passive-transfer H7N9 challenge experiment with mice. Although only a low percentage of vaccinees induced neutralizing antibody responses against the homologous vaccine strain and also H7N9, we detected strong cross-reactivity to divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination induced antibodies to both the head and stalk domains of the HA, which is in sharp contrast to seasonal inactivated vaccines. Finally, we were able to show that both neutralizing and nonneutralizing antibodies improved in vivo virus clearance in a passive-transfer H7N9 challenge mouse model.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Florian.krammer@mssm.edu rebecca.cox@k2.uib.no.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Asne
authors.initials: A
authors.lastname: Jul-Larsen
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Margine
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ariana
authors.initials: A
authors.lastname: Hirsh
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway Section for Infectious Diseases, Medical Department, Haukeland University Hospital, Bergen, Norway.
authors.forename: Haakon
authors.initials: H
authors.lastname: Sjursen
authors.affiliation: Public Health England, London, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Zambon
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, Norway Department of Research and Development, Haukeland University Hospital, Bergen, Norway Florian.krammer@mssm.edu rebecca.cox@k2.uib.no.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D057916:Influenza A Virus, H7N1 Subtype / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D014611:Vaccination; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C109963:hemagglutinin, avian influenza A virus