title: Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure.
abstract: Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.
authors.affiliation: Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Stephen S H
authors.initials: SS
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Banner
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: León
authors.forename: Stéphane G
authors.initials: SG
authors.lastname: Paquette
authors.forename: Barry
authors.initials: B
authors.lastname: Rubin
authors.forename: Salvatore
authors.initials: S
authors.lastname: Rubino
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelvin
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Kelvin
mesh_terms: D000818:Animals; D005289:Ferrets / Q000821:virology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification* / Q000187:drug effects / Q000276:immunology*; D013045:Species Specificity; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014765:Viral Vaccines