title: Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus.
abstract: We show in this study several novel features of T cell-based heterosubtypic immunity against the influenza A virus in mice. First, T cell-mediated heterosubtypic protection against lethal challenge can be generated by a very low priming dose. Second, it becomes effective within 5-6 days. Third, it provides protection against a very high dose challenge for >70 days. Also novel is the finding that strong, long-lasting, heterosubtypic protection can be elicited by priming with attenuated cold-adapted strains. We demonstrate that priming does not prevent infection of the lungs following challenge, but leads to earlier clearance of the virus and 100% survival after otherwise lethal challenge. Protection is dependent on CD8 T cells, and we show that CD4 and CD8 T cells reactive to conserved epitopes of the core proteins of the challenge virus are present after priming. Our results suggest that intranasal vaccination with cold-adapted, attenuated live virus has the potential to provide effective emergency protection against emerging influenza strains for several months.
authors.affiliation: Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Powell
authors.forename: Tara
authors.initials: T
authors.lastname: Strutt
authors.forename: Joyce
authors.initials: J
authors.lastname: Reome
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hollenbaugh
authors.forename: Alan D
authors.initials: AD
authors.lastname: Roberts
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
authors.forename: Richard W
authors.initials: RW
authors.lastname: Dutton
mesh_terms: D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D000818:Animals; D003080:Cold Temperature; D045142:Cross-Priming / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D010802:Phylogeny; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000276:immunology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D000939:Epitopes; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins