title: Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells.
abstract: Influenza A (H1N1) viruses of swine origin were introduced into the human population in 2009 and caused a pandemic. The disease burden in the elderly was relatively low, which was attributed to the presence of cross-reacting serum antibodies in this age group, which were raised against seasonal influenza A (H1N1) viruses that circulated before 1957. It has also been described how infection with heterosubtypic influenza viruses can induce some degree of protection against infection by a novel strain of influenza virus. Here, we assess the extent of protective immunity against infection with the 2009 influenza A (H1N1) pandemic influenza virus that is afforded by infection with a seasonal influenza A (H3N2) virus in mice. Mice that experienced a primary A (H3N2) influenza virus infection displayed reduced weight loss after challenge infection and cleared the 2009 influenza A (H1N1) virus infection more rapidly. To elucidate the correlates of protection of this heterosubtypic immunity to pandemic H1N1 virus infection, adoptive transfer experiments were carried out by using selected post-infection lymphocyte populations. Virus-specific CD8(+) T-cells in concert with CD4(+) T-cells were responsible for the observed protection. These findings may not only provide an explanation for epidemiological differences in the incidence of severe pandemic H1N1 infections, they also indicate that the induction of cross-reactive virus-specific CD8(+) and CD4(+) T-cell responses may be a suitable approach for the development of universal influenza vaccines.
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Marine L B
authors.initials: MLB
authors.lastname: Hillaire
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Stella E
authors.initials: SE
authors.lastname: van Trierum
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Joost H C M
authors.initials: JHCM
authors.lastname: Kreijtz
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Bodewes
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Martina M
authors.initials: MM
authors.lastname: Geelhoed-Mieras
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Nella J
authors.initials: NJ
authors.lastname: Nieuwkoop
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Ron A M
authors.initials: RAM
authors.lastname: Fouchier
authors.affiliation: Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.affiliation: Viroclinics Biosciences BV, Rotterdam, The Netherlands.|Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: ADME
authors.lastname: Osterhaus
authors.affiliation: Viroclinics Biosciences BV, Rotterdam, The Netherlands.|Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D012376:Rodent Diseases / Q000276:immunology / Q000821:virology