The study of novel DNA vaccines against tuberculosis Induction of pathogen-specific CTL in the mouse and monkey models of tuberculosis

• Published in: Human vaccines & immunotherapeutics Vol. 9; no. 3; pp. 515 - 525
• Main Authors: Okada, Masaji, Kita, Yoko, Nakajima, Toshihiro, Hashimoto, Satomi, Nakatani, Hitoshi, Nishimatsu, Shiho, Nishida, Yasuko, Kanamaru, Noriko, Kaneda, Yasuhumi, Takamori, Yasushi, McMurray, David, Tan, Esterlina V., Cang, Marjorie L., Saunderson, Paul, Dela Cruz, E.C.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.03.2013; Landes Bioscience
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Blood Proteins - genetics; Blood Proteins - immunology; Chaperonin 60 - genetics; Chaperonin 60 - immunology; CTL; Disease Models, Animal; Female; granulysin vaccine; HSP65 DNA+IL-12 DNA Vaccine; Humans; HVJ-Envelope; Interferon-gamma - metabolism; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-2 - metabolism; Japan; Ksp37; Macaca fascicularis; mice; Mice, Inbred BALB C; Mice, Inbred DBA; monkeys; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Research Paper; T-Lymphocytes, Cytotoxic - immunology; tuberculosis; Tuberculosis - immunology; Tuberculosis - prevention & control; Tuberculosis - therapy; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - immunology; vaccines against tuberculosis; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Japan; monkeys; HSP65 DNA+IL-12 DNA Vaccine; tuberculosis; HVJ-Envelope; CTL; Ksp37; vaccines against tuberculosis; granulysin vaccine; mice
• ISSN: 2164-5515; 2164-554X
• DOI: 10.4161/hv.23229

Results: HSP65 + IL-12 DNA vaccine showed higher protective efficacy compared with BCG in both mouse and monkey models of TB. It induced the TB-specific CTL in the mouse model of TB, while little level of activity was observed after the injection of BCG. It also showed strong therapeutic efficacy against MDR-TB. In the monkey model, the vaccine augmented the production of IFN-γ and IL-2 from PBL and the therapeutic effect was correlated with the level of IL-2. We next evaluated the potential of DNA vaccine encoding a granulysin, which is an important defensive molecule expressed by human T cells. We found that granulysin-encoding vaccine induced the differentiation of the CTL in vitro and in vivo. It also showed therapeutic efficacy against TB in the monkey as well as the mouse model. The DNA vaccine encoding a Ksp37 also induced the TB-specific CTL in vitro and in vivo in the mouse model. It augmented the production of IL-2, IFN-γ and IL-6 from T cells and spleen cells. A synergistic effect on the activation of the TB-specific CTL was observed by the combination of Ksp37 DNA vaccine with granulysin DNA vaccine. Purpose and Methods: Emergence of the multi-drug resistant (MDR) Mycobacterium tuberculosis (TB) is a big problem in the world. We have developed novel TB vaccines [DNA vaccines encoding HSP65 + IL-12, granulysin or killer-specific secretory protein of 37kDa (Ksp37)] using Hemagglutinating virus of Japan -envelope (HVJ-E). It is suggested that the activity of the TB-specific CTL is one of the most important factor for the resistance to TB and immunity for TB in chronic human TB disease. Therefore, we examined the level of activation of the TB-specific CTL after the administration of these vaccines. Conclusion: These data indicate that our novel vaccines (HSP65 + IL-12 DNA, granulysin and Ksp37) have a capability to activate the TB-specific CTL and will be very strong protective and therapeutic vaccines against TB.