title: The use of a mutant TNF-alpha as a vaccine adjuvant for the induction of mucosal immune responses.
abstract: Safe and potent adjuvants are required in order to establish effective mucosal vaccines. Cytokines are promising adjuvants because they are human-derived safe biomaterial and display immune-modulating functions. We have created a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, that exhibits high bioactivity and resistance to proteases. Here, we examined the potential of mTNF-K90R as a mucosal adjuvant. Initially, we showed that intranasal co-administration of mTNF-K90R with ovalbumin (OVA) potently produced OVA-specific Immunoglobulin (Ig) G antibodies (Abs) in serum and IgA Abs both at local and distal mucosal sites compared to co-administration with wild-type TNF-alpha. The OVA-specific immune response was characterized by high levels of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5 and IL-10 from splenocytes of immunized mice, suggesting a Th2 response. Furthermore, intranasal immunization with an antigen from influenza virus plus mTNF-K90R exhibited mucosal adjuvant activity for induction of both systemic and mucosal immune responses. Importantly, histopathological examination of the nasal tissue of mTNF-K90R treated mice detected no signs of toxicity. These findings suggest that mTNF-K90R is safe and effective mucosal adjuvant and this system may have potential application as a universal mucosal adjuvant system for mucosal vaccines improving the immune response to a variety of viral antigens.
authors: Laboratory of Pharmaceutical Proteomics, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors: Hiroyuki
authors: H
authors: Kayamuro
authors: Yasuhiro
authors: Y
authors: Abe
authors: Yasuo
authors: Y
authors: Yoshioka
authors: Kazufumi
authors: K
authors: Katayama
authors: Tetsuya
authors: T
authors: Nomura
authors: Tokuyuki
authors: T
authors: Yoshida
authors: Kohei
authors: K
authors: Yamashita
authors: Tomoaki
authors: T
authors: Yoshikawa
authors: Yuichi
authors: Y
authors: Kawai
authors: Tadanori
authors: T
authors: Mayumi
authors: Takachika
authors: T
authors: Hiroi
authors: Norio
authors: N
authors: Itoh
authors: Kazuya
authors: K
authors: Nagano
authors: Haruhiko
authors: H
authors: Kamada
authors: Shin-ichi
authors: S
authors: Tsunoda
authors: Yasuo
authors: Y
authors: Tsutsumi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects* / Q000276:immunology*; D009154:Mutation; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines