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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	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.
Spatial Coverage	Japan
Description	Author Affiliation: Okada M ( Clinical Research Center)
Abstract	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-Î³ 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-Î³ 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.
File Format	HTM / HTML
ISSN	21645515
e-ISSN	2164554X
Journal	Human Vaccines & Immunotherapeutics
Issue Number	3
Volume Number	9
Language	English
Publisher	Taylor & Francis
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Immunology Discipline Therapeutics Bacterial Proteins Immunology Chaperonin 60 T-lymphocytes, Cytotoxic Tuberculosis Vaccines Tuberculosis Prevention & Control Therapy Vaccines, Dna Animals Antigens, Differentiation, T-lymphocyte Genetics Blood Proteins Disease Models, Animal Interferon-gamma Secretion Interleukin-12 Interleukin-2 Macaca Fascicularis Mice, Inbred Balb C Mice, Inbred Dba Mycobacterium Tuberculosis Administration & Dosage Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Pharmacology

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