Development of new vaccine against pathogenic mycobacteria
| Project/Area Number |
17590408
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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 | National Institute of Infectious Diseases |
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Principal Investigator |
MAKINO Masahiko National Institute of Infectious Diseases, Department of Microbiology, Director (60238889)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Yumi National Institute of Infectious Diseases, Department of Microbiology, Senior Research Scientist (90311399)
YAMAZAKI Toshio National Institute of Infectious Diseases, Department of Microbiology, Senior Research Scientist (20230401)
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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 |
¥3,640,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Preventive Medicine / Bacteria / Immunology / Molecular Biology / Animal |
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| Research Abstract |
The activation of T lymphocytes inhibits the intracellular and intercellular multiplication of Mycobacterium leprae. Therefore, leprosy provides a useful model for the development of vaccine against pathogenic mycobacterial infection. First of all, we identified major membrane protein (MMP)-II as one of the immunodominant antigens of M. leprae. The recombinant MMP-II protein recognized the TLR2 molecules expressed on the surface of antigen-presenting cells and strongly activated both dendritic cells (DC) and macrophages. The DC pulsed with MMP-II activated autologous naive CD4^+ T cells and naive CD8^+ T cells obtained from healthy individuals. Further, memory type T lymphocytes obtained from paucibacillary (PB) leprosy patients responded to MMP-II and produced higher amount of IFN-γ than those from healthy individuals. These results suggest that T cells in PB leprosy are primed with MMP-II in vivo. In addition, macrophages produced from monocytes in the presence of GM-CSF and infected
… More
with M. leprae activated T lymphocytes. Then, we produced a recombinant BCG (BCG-SM) that secretes MMP-II intracytosollicaly in host cells. DC infected with BCG-SM more strongly activated autologous naive CD4^+ T lymphocytes to produce IFN-γ than those infected with vector control BCG. Further, while vector control BCG did not activate naive CD8^+ T lymphocytes, BCG-SM induced a significant production of IFN-γ from naive CD8^+ T lymphocytes. BCG-SM also induced GM-CSF production by macrophages and, through the GM-CSF production, BCG-SM-infected macrophages activated CD4^+ T lymphocytes. C57BL/6 mice infected with BCG-SM 13 weeks before, efficiently produced memory T lymphocytes which react to MMP-II in vitro. Finally we intradermally vaccinated C57BL/6 mice with either vector control BCG or BCG-SM and, four weeks later, we challenged to the vaccinated mice with M. leprae. The BCG-SM vaccination was more efficiently inhibited the multiplication of M leprae in vivo than vector control BCG. Taken together, we successfully produced more efficient BCG than parent BCG in inhibiting M. leprae growth. Less
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] ハンセン病基礎医学研究のトピックス2005
Author(s)
牧野正彦, 鈴木幸一, 福富康夫, 山下康子, 前田百美, 宮本友司, 向井 徹, 中田 登, 甲斐雅規, 山崎利雄, 儀同政一, 松岡正典
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Journal Title
Jpn.J.Leprosy 74
Pages: 3-22
NAID
Related Report
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