The study of the mechanism of therapeutic efficacy of novel vaccines on Tuberculosis-infection and the induction of cytotoxic T cells by the vaccines

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(1)We have developed a novel therapeutic tuberculosis (TB) vaccine ; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-envelope (HSP65+IL-12/HVJ). This vaccine induced CD8^+ cytotoxic T-cell specific for TB antigen.(2)This vaccine exerted therapeutic efficacy in the TB-infected cynomolgus monkeys as well as mice.(3)Granulysin augmented in vitro and in vivo induction of CTL. Thus, it was demonstrated that granulysin is CTL differentiation factor. Furthermore, in the presence of IL-6 or IL-2 the in vitro and in vivo induction by granulysin was synergistically enhanced.(4)We established granulysin transgenic mice.