The use of a mutant TNF-α as a vaccine adjuvant for the induction of mucosal immune responses

• Published in: Biomaterials 2009-10, Vol.30 (29), p.5869-5876
• Main Authors: Kayamuro, Hiroyuki, Abe, Yasuhiro, Yoshioka, Yasuo, Katayama, Kazufumi, Nomura, Tetsuya, Yoshida, Tokuyuki, Yamashita, Kohei, Yoshikawa, Tomoaki, Kawai, Yuichi, Mayumi, Tadanori, Hiroi, Takachika, Itoh, Norio, Nagano, Kazuya, Kamada, Haruhiko, Tsunoda, Shin-ichi, Tsutsumi, Yasuo
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Advanced Basic Science; Animals; Bioactivity; Cytokine; Dentistry; Female; Immunity, Innate - drug effects; Immunity, Innate - immunology; Immunomodulation; Influenza virus; Mice; Mice, Inbred BALB C; Mucosa; Mucous Membrane - drug effects; Mucous Membrane - immunology; Mutation; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Vaccines - administration & dosage; Vaccines - immunology
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.07.009

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-α (TNF-α), 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-α. 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.