2004 Fiscal Year Final Research Report Summary
Establishment of Novel (DNA-recombinant BCG-, and fusion protein-)vaccination against Tuberculosis and analysis of novel differentiation mechanism of cytotoxic T cell
| 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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| Keywords | HSP65+IL-12 DNA / Tuberculosis / CTL / granulysin / recombinant BCG / CTL differentiation factor / in vivo / mouse |
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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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Research Products
(68 results)
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[Journal Article] The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice.2005
Author(s)
Okada M, Takemoto Y, Okuno Y, Hashimoto S, Yoshida S, Fukunaga Y, Tanaka T, Kita Y, Kuwayama S, Muraki Y, Kanamaru N, Takai H, Okada C, Sakaguchi Y, Furukawa I, Yamada K, Matsumoto M, Kase T, Demello D.E., Peiris JSM, Chen P.J., Yamamoto N, Yoshinaka Y, Nomura T, Ishida I, Morikawa S, Tashiro M, Sakatani M.
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Journal Title
Vaccine 23(17-18)
Pages: 2269-2272
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel recombinant BCG and DNA-vaccination against tuberculosis in a cynomolgus monkey model.2005
Author(s)
Kita Y, Tanaka T, Yoshida S, Ohara N, Kaneda Y, Kuwayama S, Muraki Y, Kanamaru N, Hashimoto S, Takai H, Okada C, Fukunaga Y, Sakaguchi Y, Furukawa I, Yamada K, Inoue Y, Takemoto Y, Naito M, Yamada T, Matsumoto M, McMurray DN, Cruz EC, Tan EV, Abalos RM, Burgos JA, Gelber R, Skeiky Y, Reed S, Sakatani M, Okada M.
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Journal Title
Vaccine 23(17-18)
Pages: 2132-2135
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The Development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice.2004
Author(s)
Okada M, Takemoto Y, Okuno Y, Hashimoto S, Fukunaga Y, Tanaka T, Kita Y, Kuwayama S, Muraki Y, Kanamaru N, Takai H, Okada C, Sakaguchi Y, Furukawa I, Yamada K, Yoshida S, Matsumoto M, Kase T, deMello DE, Peiris JSM, Chen PJ, Yamamoto N, Yoshinaka Y, Nomura T, Ishida I, Morikawa S, Tashiro M, Sakatani M.
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Journal Title
Immunology 2004. MEDIMOND International Proceedings. Immunology 2004
Pages: 449-452
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel (Recombinant BCG- and DNA) Vaccination against Tuberculosis using Cynomolgus Monkey.2004
Author(s)
Kita Y, Tanaka T, Yoshida S, Ohara N, Kaneda Y, Kuwayama S, Muraki Y, Kanamaru N, Hashimoto S, Takai H, Okada C, Fukunaga Y, Sakaguchi Y, Furukawa I, Yamada K, Inoue Y, Takemoto Y, Naito M, Yamada T, Matsumoto M, Cruz EC, Tan EV, Abalos M, Young LJ, Burgos JA, Gelber R, Skeiky Y, Reed S, Sakatani M, Okada M.
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Journal Title
Immunology 2004. MEDIMOND International Proceedings. Immunology 2004
Pages: 403-406
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Specific detection of tuberculosis infection : an interferon-gamma-based assay using new antigens.2004
Author(s)
Mori T, Sakatani M, Yamagishi F, Takashima T, Kawabe Y, Nagao K, Shigeto E, Harada N, Mitarai S, Okada M, Suzuki K, Inoue Y, Tsuyuguchi K, Sasaki Y, Mazurek GH, Tsuyuguchi I.
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Journal Title
Am J Respir Crit Care Med. 70(1)
Pages: 59-64
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Induction of protective cellular immunity against Mycobacterium tuberculosis using a DNA vaccine encoding MPB51 antigen carried by attenuated suicide Listeria monocytogenes and identification of T-cell epitopes of the antigen.2003
Author(s)
Koide Y, Miki K, Nagata T, Suzuki M, Aoshi T, Tanaka T, Kim Y-H, Uchijima M, Ohara N, Okada M.
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Journal Title
Thirty-eighth Research Conference on Tuberculosis and Leprosy, US-Japan Cooperative Medical Science Program 32
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel (recombinant BCG- and DNA-) vaccination against tuberculosis.2003
Author(s)
Okada M, Tanaka T, Inoue Y, Matumoto K, Yoshida S, Ohara N, Naito M, Yamada T, Kaneda Y, Matsumoto M, E.C.dela Cruz, E.V.Tan, Skeiky Y, Reed S.Sakatani M.
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Journal Title
Keystone Symposia 93
Pages: 335
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel (Recombinant BCG- and DNA- )Vaccination against Tuberculosis.2003
Author(s)
Okada M, Tanaka T, Inoue Y, Takemoto Y, Yoshida S, Ohara N, Naito M, Yamada T, Kaneda Y, Matsumoto M, E.C.derla Cruz, E.V.Tan, R.M.Abalos, L.J.Young, J.A.Burgos, Skeiky Y, Reed S, Sakatani M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel (Recombinant BCG- and DNA- )Vaccination against Tube rculosis.2003
Author(s)
Okada M, Tanaka T, Inoue Y, Takemoto Y, Yoshida S, Ohara N, Naito M, Yamada T, Kaneda Y, Matsumoto M, Cruz EC, Tan EV, Abalos RM, Young LJ, Burgos JA, Skeiky Y, Reed S, Sakatani M.
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Journal Title
Thirty-Eighth Tuberculosis and Leprosy Research Conference US-JAPAN Cooperative Medical Science Program 191
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel (Recombinant BCG- and DNA-)Vaccination against Tuberculosis.2003
Author(s)
Okada M, Tanaka T, Inoue Y, Takemoto Y, Yoshida S, Ohara N, Naito M, Yamada T, Kaneda Y, Matsumoto M, E.V.Tan, E.C.Dela, Cruz, R.M.Abalos, L.J.Young, J.A.Burgos, Skeiky Y, Reed S, Sakatani M.
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Journal Title
The Awaji International Forum Infection Immunity. 3
Pages: 126
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] L523S, an RNA-binding protein as a potential therapeutic target for lung cancer.2003
Author(s)
Wang T, Fan L, Watanabe Y, McNeill PD, Moulton GG, Bangur C, Fanger GR, Okada M, Inoue Y, Parsing DH, Reed SG.
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Journal Title
Br J Cancer. 88(6)
Pages: 887-894
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel (recombinant BCG- and DNA-)vaccination against tuberculosis.2002
Author(s)
Okada M, Tanaka T, Inoue Y, Matsumoto K, Kita Y, Kimura K, Yoshida S, Ohara N, Naito M, Yamada T, Kaneda Y, Matsumoto M, Matsumoto S, Skeiky Y, Reed S, Sakatani M.
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Journal Title
Thirty-Seventh Tuberculosis and Leprosy Research Conference.
Pages: 171-175
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel DNA and Recombinant BCG Vaccination against Tuberculosis by the Augmentation of Cytotoxic Activity.2002
Author(s)
Okada M, Yoshida S, Ohara N, Yamada T, Kaneda Y, Tanaka T, Kita Y, Kuwayama S, Muraki Y, Inanaga Y, Kanamaru N, Inoue Y, Matsumoto M, Kimura K, Sakatani M, Mori T.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] (recombinant BCG- and DNA-) vaccination against tuberculosis.2002
Author(s)
Okada M, Tanaka T, Inoue Y, Matsumoto K, Yoshida S, Ohara N.Naito M, Yamada T, Kaneda Y, Matsumoto M, Matsumoto S, Skeiky Y, Reed S, Sakatani M.
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Journal Title
The Awaji International Forum on Infection and Immunity p-091
Description
「研究成果報告書概要(欧文)」より
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