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Identification of low-molecular-mass secretory proteins of Mycobacterium tuberculosis and the application to development of anti-tuberculosis vaccines

Research Project

Project/Area Number 20590438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

NAGATA Toshi  Hamamatsu University School of Medicine, 医学部, 教授 (90275024)

Co-Investigator(Kenkyū-buntansha) TSUJIMURA Kunio  浜松医科大学, 医学部, 准教授 (10227407)
KOIDE Yukio  浜松医科大学, 医学部, 理事 (30126809)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsDNAワクチン / 結核 / 低分子量分泌タンパク / T細胞エピトープ
Research Abstract

We identified here murine and human dominant T-cell epitopes of three low-molecular-mass secretory proteins, CFP11 (Rv2433c), CFP17 (Rv1827), TB18.5 (Rv0164) of Mycobacterium tuberculosis. Plasmid DNAs encoding these proteins were immunized to two inbred mice and HLA-DRB1^*0401 transgenic mice. T-cell epitopes were determined based on IFN-γ production from immune spleen cells. The results obtained here is feasible for analysis of the role of antigen-specific T cells during M.tuberculosis infection and the vaccine development.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (49 results)

All 2011 2010 2009 2008 Other

All Journal Article (26 results) (of which Peer Reviewed: 23 results) Presentation (21 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70.2011

    • Author(s)
      Uto T, Tsujimura K, Uchijima M, Seto S, Nagata T, Suda T, Chida K, Nakamura H, Koide Y
    • Journal Title

      FEMS Immunol.Med.Microbiol. 61

      Pages: 189-196

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70.2011

    • Author(s)
      Uto T, Tsujimura K, Uchijima M, Seto S, Nagata T, Suda T, Chida K, Nakamura H, Koide Y.
    • Journal Title

      FEMS Immunol.Med.Microbiol.

      Volume: 61 Pages: 189-196

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 結核菌に対するT細胞誘導ワクチンの試み2010

    • Author(s)
      永田年、小山幸夫
    • Journal Title

      日本細菌学雑誌 65(2)

      Pages: 309-324

    • NAID

      10028050121

    • Related Report
      2010 Final Research Report
  • [Journal Article] Identification of murine T-cell epitopes on low-molecular-mass secretory proteins (CFP11, CFP17, and TB 18.5) of Mycobacterium tuberculosis.2010

    • Author(s)
      Eweda G, Suzuki D, Nagata T, Tsujimura K, Koide Y
    • Journal Title

      Vaccine 28

      Pages: 4616-4625

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of specific CD8+ Tcells against intracellular bacteria by CD8+ T-cell-oriented immunzation approaches.2010

    • Author(s)
      Nagata T, Koide Y
    • Journal Title

      J Biomed Biotechnol

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of murine T-cell epitopes on mycobacterial DNA-binding 1(MDP 1)using DNA vaccination.2010

    • Author(s)
      Suzuki D, Nagata T, Ewda G, Matsumoto S, Matsumoto M, Tsuiimura K, Koide Y
    • Journal Title

      Vaccine 28

      Pages: 2020-2025

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis using MPT51 overlapping peptides screening and DNA vaccination.2010

    • Author(s)
      Wang L-X, Nagata T, Tsuiimura K, Uchijima M, Seto S, Koide Y
    • Journal Title

      Vaccine 28

      Pages: 2026-2031

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenicity of latency-associated antigens of Mycobacterium tuberculosis in DNA-vaccinated mice.2010

    • Author(s)
      Yamamura Y, Tsuiimura K, Seto S, Uchijima M, Hozumi H, Nagata T, Koide Y
    • Journal Title

      Procedia in Vaccinology 3

      Pages: 19-26

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of murine T-cell epitopes on low-molecular-mass secreted protein (CFP11, CFP17, and TB18.5) of Mycobacterium tuberculosis with DNA immunization.2010

    • Author(s)
      Eweda G, Suzuki D, Nagata T, Tsujimura K, Koide Y.
    • Journal Title

      Vaccine

      Volume: 28 Pages: 4616-4625

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenicity of latency-associated antigens of Mycobacterium tuberculosis in DNA-vaccinated mice.2010

    • Author(s)
      Yamamura Y, Tsujimura K, Seto S, Uchijima M, Hozumi H, Nagata T, Koide Y.
    • Journal Title

      Procedia Vaccinol.

      Volume: 3 Pages: 19-26

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of specific CD8^+ T cells against intracellular bacteria by CD8+ T-cell-oriented immunization approaches.2010

    • Author(s)
      Nagata T, Koide Y.
    • Journal Title

      J.Biomed.Biotechnol.

      Volume: ID 764542(online)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70.2010

    • Author(s)
      永田年、小出幸夫
    • Journal Title

      日本細菌学会雑誌

      Volume: 65 Pages: 309-324

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Characterization of murine T-cell epitopes on mycobacterial DNA-binding protein 1 (MDP1) using DNA vaccination2010

    • Author(s)
      Suzuki D, Nagata T, Eweda G, Matsumoto S, Matsumoto M, Tsujimura K, Koide Y.
    • Journal Title

      Vaccine 28

      Pages: 2020-2025

    • NAID

      120005305392

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis using MPT51 overlapping peptides screening and DNA vaccination2010

    • Author(s)
      Wang L-X, Nagata T, Tsujimura K, Uchijima M, Seto S, Koide Y.
    • Journal Title

      Vaccine 28

      Pages: 2026-2031

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of anti-tumor immune responses with oligomannose-coated liposomes targeting to peritoneal macrophages.2009

    • Author(s)
      Tsuiimura K, Ikehara Y, Nagata T, Koide Y, Kojima N
    • Journal Title

      Procedia in Vaccinology 1

      Pages: 127-134

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of anti-tumor responses with oligomannose-coated liposomes targeting to peritoneal macrophages2009

    • Author(s)
      Tsujimura K, Ikehara Y, Nagata T, Koide Y, Kojima N.
    • Journal Title

      Procedia in Vaccinology 1

      Pages: 127-134

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo hierarchy of individual T-cell epitope-specific helper T-cell subset against an intracellular bacterium.2008

    • Author(s)
      Nagata T, Aoshi T, Uchijima M, Koide Y
    • Journal Title

      Vaccine 26

      Pages: 5123-5127

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of HLA-A*0201-restricted T-cell epitope on the MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis, by MPT51 overlapping peptide screening.2008

    • Author(s)
      Aoshi T, Nagata T, Suzuki M, Uchijima M, Hashimoto D, Rafiei A, Suda T, Chida K, Koide Y
    • Journal Title

      Infect Immun 76

      Pages: 1565-1571

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-infective vaccine strategies.2008

    • Author(s)
      Nagata T, Koide Y
    • Journal Title

      In Liu D (ed.) Handbook of Listeria monocytogenes CRC Press

      Pages: 449-480

    • Related Report
      2010 Final Research Report
  • [Journal Article] Intratracheal administration of third-generation lentivirus vector encoding MPT51 from Mycobacterium tuberculosis induces specific CD8+ T-cell responses in the lung.2008

    • Author(s)
      Hashimoto D, Nagata T, Uchijima M, Seto S, Suda T, Chida K, Miyoshi H, Nakamura H, Koide Y
    • Journal Title

      Vaccine 26

      Pages: 5095-5100

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular Listeria monocytogenes induces pyroptosis in murine macrophages.2008

    • Author(s)
      Cervantes J, Nagata T, Uchijima M, Shibata K, Koide Y
    • Journal Title

      Cell Microbiol 10(1)

      Pages: 41-52

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracytosolic Listeria monocytogenes induces cell death through caspase-1 activation in murine macrophages.2008

    • Author(s)
      Cervantes J, Nagata T, Uchijima M, Shibata K, Koide Y.
    • Journal Title

      Cellular Microbiology 10 (1)

      Pages: 41-57

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of an HL A-A^*0201-restricted T-cell epitope on the MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis, by MPT51 overlapping peptide screening.2008

    • Author(s)
      Aoshi T, Nagata T, Suzuki M, Uchijima M, Hashimoto D, Rafiei A, Suda T, Chida K, Koide Y.
    • Journal Title

      Infection and Immunity 76 (4)

      Pages: 1565-1571

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo hierarchy of individual T-cell epitope-specific helper T-cell subset against an intracellular bacterium.2008

    • Author(s)
      Nagata T, Aoshi T, Uchijima M, Koide Y.
    • Journal Title

      Vaccine 26 (40)

      Pages: 5123-5127

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemokine receptor-mediated delivery of mycobacterial MPT51 protein efficiently induces antigen-specific T-cell responses.2008

    • Author(s)
      Uchijima M, Nagata T, Koide Y.
    • Journal Title

      Vaccine 26 (40)

      Pages: 5165-5169

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intratracheal administration of third-generation lentivirus vector encoding MPT51 from Mycobacterium tuberculosis induces specific CD8+T-cell responses in the lung.2008

    • Author(s)
      Hashimoto D, Nagata, T, Uchijima M, Seto s, Chida K, Miyoshi H, Nakamura H, Koide Y.
    • Journal Title

      Vaccine 26 (40)

      Pages: 5095-5100

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of murine T-cell epitopes on low-molecular-mass secreted proteins of Mycobacterium tuberculosis. Keystone Symposia, Tuberculosis2011

    • Author(s)
      Nagata T, Eweda G, Suzuki D, Tsuiimura K, Koide Y
    • Organizer
      Immunology, Cell Biology and Novel Vaccination Strategies, Vancouver
    • Place of Presentation
      USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Identification of murine T-cell epitopes on low-molecular-mass secreted proteins of Mycobacterium tuberculosis.2011

    • Author(s)
      Eweda G, Suzuki D, Nagata T, Tsujimura K, Koide Y.
    • Organizer
      Keystone Symposia Tuberculosis : Immunology, Cell Biology and Novel Vaccination Strategies
    • Place of Presentation
      Vancouver, BC, Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of murine T-cell epitopes on low-molecular-mass secreted proteins (CFP11, CFP17, and TB18.5) of Mycobacterium tuberculosis with DNA immunization.2010

    • Author(s)
      Eweda G, Suzuki D, Nagata T, Tsuiimura K, Koide Y
    • Organizer
      DNA Vaccines 2010, New Orleans
    • Place of Presentation
      USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Immunogenicity of dormancy-related antigens of Mycobacterium tuberculosis in DNA-vaccinated mice.2010

    • Author(s)
      Yamamura Y, Tsujimura K, Uchijima M, Seto S, Nagata T, Koide Y
    • Organizer
      DNA Vaccines 2010, New Orleans
    • Place of Presentation
      USA
    • Related Report
      2010 Final Research Report
  • [Presentation] DNAワクチンを用いた結核菌低分子量分泌蛋白のマウスT細胞エピトープの同定2010

    • Author(s)
      永田年、エウィーダガダ、鈴木大介、辻村邦夫、小出幸夫
    • Organizer
      第83回日本細菌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Identification of murine T-cell epitopes on low-molecular-mass secreted protein (CFP11, CFP17, and TB18.5) of Mycobacterium tuberculosis with DNA immunization2010

    • Author(s)
      エウィーダガダ, 鈴木大介, 永田年, 辻村邦夫, 小出幸夫
    • Organizer
      DNA Vaccines 2010
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Immunogenicity of dormancy-related antigens of Mycobacterium tuberculosis in DNA-vaccinated mice2010

    • Author(s)
      Yamamura Y, Tsujimura K, Uchijima M, Seto S, Nagata T, Koide Y.
    • Organizer
      DNA Vaccines 2010
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] 結核菌HSP70-MPT51融合ワクチンはMPT51特異的CD4陽性T細胞反応を増強する2010

    • Author(s)
      右藤智啓, 内嶋雅人, 瀬戸真太郎, 永田年, 辻村邦夫, 小出幸夫
    • Organizer
      第83回日本細菌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] MIP-1αと結核菌MPT51融合型DNAワクチンは抗原特異的CD8^+ T細胞を強く誘導する2010

    • Author(s)
      内嶋雅人, 永田年, 辻村邦夫, 小出幸夫
    • Organizer
      第83回日本細菌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] DNAワクチンを施行したマウスにおける結核菌の潜伏感染関連抗原の免疫原性2009

    • Author(s)
      山村泰弘、瀬戸真太郎、内嶋雅人、穂積宏尚、永田年、辻村邦夫、小出幸夫
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] DNAワクチンを用いた結核菌低分子量分泌蛋白のマウスT細胞エピトープの同定2009

    • Author(s)
      永田年、鈴木大介、辻村邦夫、小出幸夫
    • Organizer
      第82回日本細菌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] DNAワクチンを用いたMycobacterial DNA binding protein 1(MDP1)のマウスT細胞エピトープの同定2009

    • Author(s)
      鈴木大介, 永田年, 辻村邦夫, 松本壮吉, 小出幸夫
    • Organizer
      第82回日本細菌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Characterization of an HLA-DR4-restricted CD4+ T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis by DNA vaccination.2008

    • Author(s)
      Wang LX, Nagata T, Koide Y
    • Organizer
      DNA Vaccines 2008, Las Vegas
    • Place of Presentation
      USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Characterization of murine T-cell epitopes in mycobacterial DNA-binding protein 1.2008

    • Author(s)
      Suzuki D, Nagata T, Koide Y
    • Organizer
      DNA Vaccines 2008, Las Vegas
    • Place of Presentation
      USA
    • Related Report
      2010 Final Research Report
  • [Presentation] ケモカイン融合型DNAワクチンにより誘導される抗原特異的CD8^+およびCD4^+細胞の解析2008

    • Author(s)
      内嶋雅人、永田年、辻村邦夫、小出幸夫
    • Organizer
      第82回日本細菌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report
  • [Presentation] MDP1タンパクのマウスT細胞エピトープの解析2008

    • Author(s)
      鈴木大介、永田年、松本壮吉、小出幸夫
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] 結核菌抗原MPT51にHeat-shock protein 70(HSP70)を結合させた分子融合型DNAワクチンは抗原特異的T細胞を効率よく誘導する2008

    • Author(s)
      右藤智啓、内嶋雅人、永田年、辻村邦夫、小山幸夫
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] MIP-1α-MPT51融合型DNAワクチンにより誘導される抗原特異的CD8^+およびCD4^+T細胞の解析2008

    • Author(s)
      内嶋雅人、永田年、辻村邦夫、柴田清、小山幸夫
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] Characterization of murine T-cell epitopes in mycobacterial DNA-binding protein 12008

    • Author(s)
      Suzuki D, Nagata T, Matsumoto S, Koide Y.
    • Organizer
      DNA Vaccines 2008
    • Place of Presentation
      Las Vegas, NV, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Characterization of human HLA-DR4-restricted CD4+ T-cell epitope on MPT5 1 protein, a major secreted protein derived from Mycobacterium tuberculosis.2008

    • Author(s)
      Wang L-X, Nagata T, Koide Y.
    • Organizer
      DNA Vaccines 2008
    • Place of Presentation
      Las Vegas, NV, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Characterization of murine T-cell epitopes in mycobacterial DNA-binding protein 12008

    • Author(s)
      Suzuki D, Nagata T, Matsumoto S, Koide Y.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www2.hama-med.ac.jp/w1c/basic/environ/Welcome.html

    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 新規ペプチド及びこのペプチドから成る抗結核菌ワクチン2009

    • Inventor(s)
      小出幸夫、鈴木美奈、青枝大貴、永田年
    • Filing Date
      2009-03-12
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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