| Project/Area Number |
14570294
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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 |
Immunology
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| Research Institution | Clinical Research Center, National Hospital Organization, Kinki-Chuo Chest Medical Center |
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Principal Investigator |
OKADA Masaji Clinical Research Center National Hospital Organization Kinki-Chuo Chest Medical Center, The General Director, 臨床研究センター, 臨床研究センター長 (40160684)
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| Co-Investigator(Kenkyū-buntansha) |
OHARA Naoya Nagasaki Univ.Grad.Sch.Biomed.Sci, Div.of Microbiol.Oral Infect., Assistant Professor, 歯学部, 助教授 (70223930)
YOSHIDA Shigeto Jichi.Medical School, Dept.Infectious Immunity, Assistant Professor, 医学部, 講師 (10296121)
SUZUKI Katsuhiro Clinical Research Center National Hospital Organization Kinki-Chuo Chest Medical Center, Director, 臨床研究センター・感染症研究部, 部長 (00206468)
INOUE Yoshikazu Clinical Research Center National Hospital Organization Kinki-Chuo Chest Medical Center, Director, 臨床研究センター・呼吸不全 難治性肺疾患研究部, 部長 (90240895)
MINAMOTO Seijiro Clinical Research Center National Hospital Organization Kinki-Chuo Chest Medical Center, Head, 臨床研究センター・感染症研究部, 室長 (40212237)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | HSP65+IL-12 DNA / Tuberculosis / CTL / granulysin / recombinant BCG / CTL differentiation factor / in vivo / mouse / granulysin |
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| Research Abstract |
〔Abstract〕
1.The production of cytotoxic T cell differentiation factors (IL-6,IL-2,and IFN-Y,) were inhibited in the culture supernatants from patients with tuberculosis. Furthermore, it was demonstrated that the expression of granulysin (cytotoxic protein against tuberculosis) protein in CD3^+ CD8^+ CTL from TB patients was suppressed in comparison with the granulysin expression on CD8^+ CTL from healthy volunteers.
2.Two novel TB vaccines ; a DNA vaccine combination expressing mycobacterial heat shock protein 65(HSP65) and interleukin-12(IL-12) by using the hemagglutinating virus of Japan(HVJ)-liposome (HSP65+IL-12/HVJ), have been developed. These vaccines provide remarkable protective efficacy in mouse and guinea pig models, as compared to the current by available BCG vaccine.HSPGS DNA+IL-12 DNA vaccination were 100 fold more efficient than parental BCG Tokyo vaccination, on the elimination of M. TB in lungs, liver, and spleen of BALB/c mice. In the present study, our studies were extended to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis, to evaluate the HSP65+IL-12 vaccine. Vaccination with HSP65+IL-12 DNA provided better protective efficacy as assessed by the Erythrocyte Sedimentation Rate, chest X-ray findings, body weight and immune responses (IFN-y, IL-2, IL-6 production, and lymphocyte proliferation of cynomolgus monkey), than BCG. Most importantly, HSP65+IL-12 DNA vaccine resulted in an increased survival for over a year. This is the first report of successful DNA vaccination against M. tuberculosis in the monkey model.
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