title: Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus.
abstract: A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W(v) mice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.
authors.affiliation: Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayamuro
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Shuhei
authors.initials: S
authors.lastname: Arita
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nomura
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Kubota-Koketsu
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Norio
authors.initials: N
authors.lastname: Itoh
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagano
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology* / Q000378:metabolism; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011994:Recombinant Proteins