| Project/Area Number |
17390126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KOIDE Yukio Hamamatsu University School of Medicine, School of Medicine, Professor (30126809)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Toshi Hamamatsu University School of Medicine, School of Medicine, Professor (90275024)
UCHIJIMA Masato Hamamatsu University School of Medicine, School of Medicine, Assistant Professor (20252174)
CHIDA Kingo Hamamatsu University School of Medicine, School of Medicine, Associate Professor (40197611)
SUDA Takafumi Hamamatsu University School of Medicine, School of Medicine, Assistant Professor (30291397)
青枝 大貴 浜松医科大学, 医学部, 助手 (10324344)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,020,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥720,000)
Fiscal Year 2007: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2006: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | Mycobacterium tuberculosis / Vaccine / Lentivirus vector / Chemokine / T-cell epitope |
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| Research Abstract |
We have reported, for the first time, that MPT51, a major secretory protein of Mycobacterium tuberculosis (MTB), is able to induce protective immunity against MTB infection. The aim of this research is, therefore, to develop novel vaccines using MTP51 for use heterologous vaccination in conjunction with BCG and to identify T cell epitopes to estimate efficacy of the vaccine.
1. Novel vaccines: (1) Third-generation lentivirus vector as an in vivo-administered T-cell vaccine against tuberculosis. Intratracheal administration of the lentivirus vector encoding MPT51 of Mycobacterium tuberculosis could induce MPT51-specific CD8+ T cells in the mediastinal lymph nodes 2 weeks after the administration. The vaccination could generate MPT51-specific memory CD8+ T cells in the lung, but not in the lymph nodes. Further, a single intratracheal immunization of MPT51 lentiviral vaccine decreased significantly the number of virulent M tuberculosis in the lung after intratracheal challenge of the bacillus.(2) a DNA vaccine encoding fusion protein consisting of CCL3 (MIP-1α) and MPT51 on induction of specific CD8+ T cells. The DNA vaccine encoding the fusion protein could induce significantly higher number of the antigen specific CD8+ T-cells in mice than DNA vaccine encoding MPT51 alone,suggesting that DNA vaccine encoding MIP-la-antigen fusion protein is able to be efficiently internalized into antigen-presenting cells via the chemokine receptor and induce higher level of antigen specific CD8+ T cell responses.
2. T-cell epitopes of MPT51: Using lymphocytes from both HLA transgenic mice and humans, we identified HLA-A*0201 and HLA-DR4-restricted T-cell epitopes. Employing peptide overlapping library of MPT51 and computer algorithm, we revealed that MPT51(53-62) and (191-202) are HLA-A*0201 and HLA-DR4-restricted T-cell epitopes, respectively.
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