title: Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice.
abstract: It has been known that influenza A virus infection induces a cross-protective immunity against infection by viruses with different subtypes of viral envelope proteins, hemagglutinin (HA) and neuraminidase (NA). This heterosubtypic immunity is generally mediated by cytotoxic T lymphocytes (CTL) reactive to specific epitopes in the viral internal proteins, such as nucleoprotein and matrix protein. By contrast, immunization with inactivated virus antigens has been thought to be unable to generate heterosubtypic immunity, since inactivated antigens do not usually induce CTL responses. However, we show that intranasal immunization with formalin-inactivated intact virus, but not ether-split vaccines, induced a broad spectrum of heterosubtypic protective immunity in mice. The protection may be mediated by the mucosal immune response, most likely secretory IgA antibodies to the viral proteins. This approach may overcome limitations in the efficacy of inactivated influenza vaccines and confer potent immunity to humans against viruses with new pandemic potential.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan. atakada@ims.u-tokyo.ac.jp
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsushita
authors.forename: Ai
authors.initials: A
authors.lastname: Ninomiya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D003429:Cross Reactions; D005260:Female; D005557:Formaldehyde; D006386:Hemagglutination Tests; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D051379:Mice; D009439:Neuraminidase / Q000032:analysis / Q000276:immunology; D015164:Vaccines, Inactivated; D010948:Viral Plaque Assay
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D005557:Formaldehyde; D009439:Neuraminidase