Characterization of Novel Mucosal Modulator for IgA

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A major goal of this International Collaboration Research Project supported by the Ministry of Education, Science, Sports and Culture of Japan was to develop new generation vaccine, namely "Mucosal Vaccine" for the prevention of infectious diseases in next century. To accomplish this goal, our efforts was focused on the development and characterization of new mucosal adjubant since it has been shown the oral and/or nasal immunization of protein vaccine antigen required co-administration of mucosal enhancing molecule for the induction of maximum antigen-specific immune response. Together with investigators in Immunobiology Vaccine Center the University of Alabama at Birmingham (Prof. Jerry R. McGhee) and National Institute of Infectious Diseases of Tokyo (Director, Yoshifumi Takeda), we have successfully generated two forms of mutant cholera toxin (mCT) known as S61F and E112K which do not possess toxicity but maintain adjuvant activity. These two mCTs maintained an ability of native fo … More rm of CT for supporting Th2 type cell driven mucosal IgA and systemic IgG responses. When these mCT were given together with new S. pneumoniae vaccine antigen candidate, PspA to mice via nasal route, high levels of antigen-specific secretory IgA and serum IgG antibody provided protective immunity against in vivo challenge. These findings suggested that S61F and E112K can be used as new generation of mucosal adjuvant for the induction of protective immunity against different forms of infection. Our current effort is also aimed to the elucidation of molecular and cellular mechanisms for the mucosal adjuvant activity of mCT. Our recent results suggest that mCT regulate expression of co-stimalatory molecules, such as B7-1 and B7-2 on antigen presenting cells for the induction and regulation of antigen-specific immune response. Finally, our study is recently extended to examine potential application of cytokine for mucosal adjuvant. It was interesting to note that nasally co-administered IL-12 supported antigen-specific-IgA immune responses. This finding provide new possibility that IL-12 can be used as mucosal cytokine for the induction and regulation of vaccine antigen-specific immune response in vivo. These interesting and important findings wore published in high quality international journals (e. g., J. Exp. Med., Proc. Natl. Acad. Sci. USA., Nature Med., J. Immunol. and etc). Through this international collaboration project, a total of 44pepars was published in these journals by our efforts provided in this two years grant funded period. Less