title: Alum-adjuvanted H5N1 whole virion inactivated vaccine (WIV) enhanced inflammatory cytokine productions.
abstract: Alum-adjuvanted H5 whole virion inactivated vaccine (WIV) was licensed for adults in Japan but induced marked febrile reactions with significantly stronger antibody responses in children. In this study, the mechanisms behind the different responses were investigated. Lymphocytes were obtained from 25 healthy subjects who were not immunized with H5 vaccine, to examine the innate immune impact of the various vaccine formulations, analyzing the cytokine production profile stimulated with alum adjuvant alone, alum-adjuvanted H5 WIIV, plain H5 WIV, and H5 split vaccine. Alum adjuvant did not induce cytokine production, but H5 split induced IFN-γ and TNF-α. H5 WIV induced IL-6, IL-17, TNF-α, MCP-1, IFN-γ, and IFN-α. An extremely low level of IL-1β was produced in response to H5 WIV, and alum-adjuvanted H5 WIV enhanced IL-1β production, with similar levels of other cytokines stimulated with H5 WIV. Enhanced production of cytokines induced by alum-adjuvanted H5 WIV may be related to the higher incidence of febrile reactions with stronger immune responses in children but it should be further investigated why efficient immune responses with febrile illness were observed only in young children.
authors.affiliation: Kitasato Institute for Life Sciences, Laboratory of Viral Infection, Tokyo, Japan. tetsuo-n@lisci.kitasato-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakayama
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Kashiwagi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kawashima
authors.forename: Takuji
authors.initials: T
authors.lastname: Kumagai
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ihara
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000534:Alum Compounds / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007223:Infant; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007564:Japan; D008297:Male; D008875:Middle Aged; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C041524:aluminum sulfate