title: Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets.
abstract: Infection with seasonal influenza viruses induces a certain extent of protective immunity against potentially pandemic viruses of novel subtypes, also known as heterosubtypic immunity. Here we demonstrate that infection with a recent influenza A/H3N2 virus strain induces robust protection in ferrets against infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Prior H3N2 virus infection reduced H5N1 virus replication in the upper respiratory tract, as well as clinical signs, mortality, and histopathological changes associated with virus replication in the brain. This protective immunity correlated with the induction of T cells that cross-reacted with H5N1 viral antigen. We also demonstrated that prior vaccination against influenza A/H3N2 virus reduced the induction of heterosubtypic immunity otherwise induced by infection with the influenza A/H3N2 virus. The implications of these findings are discussed in the context of vaccination strategies and vaccine development aiming at the induction of immunity to pandemic influenza.
authors.affiliation: Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, P. O. Box 2040, 3000 CA Rotterdam, Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Bodewes
authors.forename: J H C M
authors.initials: JH
authors.lastname: Kreijtz
authors.forename: M M
authors.initials: MM
authors.lastname: Geelhoed-Mieras
authors.forename: G
authors.initials: G
authors.lastname: van Amerongen
authors.forename: R J
authors.initials: RJ
authors.lastname: Verburgh
authors.forename: S E
authors.initials: SE
authors.lastname: van Trierum
authors.forename: T
authors.initials: T
authors.lastname: Kuiken
authors.forename: R A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: A D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: G F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006651:Histocytochemistry; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D012137:Respiratory System / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007252:Influenza Vaccines