Novel vaccine strategies for induction of the lung-homing Th1 and CTL against tuberculosis
| Project/Area Number |
15590383
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 School of Medicine, Department of Microbiology, Professor, 医学部, 教授 (30126809)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Toshi School of Medicine, Department of Microbiology, Associate Professor, 医学部, 助教授 (90275024)
UCHIJIMA Masato School of Medicine, Department of Microbiology, Assistant Professor, 医学部, 助手 (20252174)
AOSHI Taiki School of Medicine, Department of Microbiology, Assistant Professor, 医学部, 助手 (10324344)
OKADA Masaji Kinki-Chuo Chest Medical Center, Director, 臨床研究センター, 部長 (40160684)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Mycobacterium tuberculosis / Vaccine / Lentiviral vector / Tetramer assay / T cells / 組換えリステリアワクチン / 経鼻免疫 / 肺指向性T細胞 / 感染防御免疫 |
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| Research Abstract |
We tried to develop vaccines to induce T cells which are able to immigrate to the lung and protect pulmonary tuberculosis. To achieve the goal, we employed the third generation lentiviral vector which shows high infection efficiency and safety in this fiscal year. We inserted the MPT51 gene, a protective antigen of Mycobacterium tuberculosis we have demonstrated, into the lentiviral vector and inoculate it intratrachealy. The results obtained are as follows ;
1.The immunization induced BALT formation in the lung. 2.GFP expression was observed in about 12 % of macrophages in the lung 2 weeks after inoculation and then GFP-expressing cells were decreased in number. 3.Using D^d/MPT 24-32 tetramer, we identified that about 1% of CD8+T cells were specific to MPT51 in the mediastinal lymph node 4.The tetramer-positive cells were detectable in the lung, but not in the spleen. 5.Cells from immunized mediastinal lymph node were able to produce high amount of IFN-□ upon the peptide stimulation.
Taken together, these results indicate that the intratracheal immunization of the lentiviral vector expressing M. tuberculosis antigens is feasible to induce lung-homing anti-tuberculosis T cells. We are currently investigating the effect of this vaccination as booster immunization when BCG is inoculated as prime immunization.
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Report
(3 results)
Research Products
(24 results)
