Novel prophylactic and therapeutic vaccine against tuberculosis

• Published in: Vaccine Vol. 27; no. 25; pp. 3267 - 3270
• Main Authors: Okada, Masaji, Kita, Yoko, Nakajima, Toshihiro, Kanamaru, Noriko, Hashimoto, Satomi, Nagasawa, Tetsuji, Kaneda, Yasufumi, Yoshida, Shigeto, Nishida, Yasuko, Nakatani, Hitoshi, Takao, Kyoko, Kishigami, Chie, Inoue, Yoshikazu, Matsumoto, Makoto, McMurray, David N, dela Cruz, E.C, Tan, E.V, Abalos, R.M, Burgos, J.A, Saunderson, Paul, Sakatani, Mitsunori
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Kidlington Elsevier Ltd 26.05.2009; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animal models; Animals; Applied microbiology; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biological and medical sciences; CD8 Antigens - immunology; Chaperonin 60; Chaperonins - genetics; Chaperonins - immunology; Clinical trials; Cynomolgus; Deoxyribonucleic acid; DNA; Drug Resistance, Multiple, Bacterial; Fundamental and applied biological sciences. Psychology; Grants; Hemagglutinating virus of Japan; HSP65 + IL-12 DNA vaccine; Immunization; Infections; Interleukin-12 - genetics; Interleukin-12 - immunology; Lung - microbiology; Macaca fascicularis; Mice; Microbiology; Mycobacterium; Spleen; Therapeutic effect; Tuberculosis; Tuberculosis - therapy; Tuberculosis Vaccines - immunology; Tuberculosis Vaccines - therapeutic use; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - immunology; Vaccines, DNA - therapeutic use; Therapeutic effect; HSP65 + IL-12 DNA vaccine; Tuberculosis; Prevention; HSP65+IL-12 DNA vaccine; Genetic vaccine; Immunotherapy
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.01.064

Abstract We have developed a novel 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 and -liposome (HSP65 + IL-12/HVJ). This vaccine provided therapeutic efficacy as well as remarkable protective efficacy via CD8+ T and CD4+ T cells in murine models compared with the saline controls, on the basis of CFU of number of multi-drug resistant TB (MDR-TB), and survival of extremely drug resistant TB (XDR-TB) challenged mice. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This vaccine exerted therapeutic efficacy (survival and immune responses) in the TB-infected monkeys. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials.