title: [Application of bioactive mutant TNF alpha to a mucosal vaccine adjuvant].
abstract: A large number of emerging pathogens, such as severe acute respiratory syndrome (SARS), human immunodeficiency virus (HIV), and influenza virus are mucosally transmitted and must cross mucosal barriers to infect the host. Thus, to induce a maximal protective effect, it is desirable to apply vaccines by the mucosal route where virus infections start. Mucosal vaccines administered either orally or nasally have been shown to be effective in inducing antigen-specific immune responses at both systemic and mucosal compartments. However the mucosal antigen-specific immune response is weak because most protein antigens can evoke only a weak immune response when they are applied mucosally. Therefore, one strategy to overcome the weakness of the immune response is a co-administration of mucosal adjuvant with the vaccine antigen. Unfortunately, the development of safe and effective mucosal adjuvant has proved to be challenging. Cytokines are promising adjuvants because they are human-derived safe material and display potent immune-modulating functions. In this regards, we have created a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, that exhibits high bioactivity and resistance to proteases. In this report, we examined the potential of mTNF-K90R as a mucosal adjuvant and evaluated its effectiveness and safety.
authors.affiliation: National Institute of Biomedical Innovation, Laboratory of Pharmaceutical Proteomics, Ibaraki, Osaka, 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: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D006801:Humans; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology*; D050505:Mutant Proteins; D019151:Peptide Library; D014409:Tumor Necrosis Factor-alpha; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D050505:Mutant Proteins; D019151:Peptide Library; D014409:Tumor Necrosis Factor-alpha; D014765:Viral Vaccines