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

• Project/Area Number: 20590438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Hamamatsu 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: ¥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)
• Keywords: DNA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.

Research Products

• [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
  • 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
  • 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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
• [Journal Article] Characterization of murine T-cell epitopes on mycobacterial DNA-binding protein 1 (MDP1) using DNA vaccination (2010)
  • 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
  • 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, Tsujimura K, Uchijima M, Seto S, Koide Y.
  • Journal Title: Vaccine 28 Pages: 2026-2031
  • 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
  • Peer Reviewed
• [Journal Article] Induction of anti-tumor responses with oligomannose-coated liposomes targeting to peritoneal macrophages (2009)
  • Author(s): Tsujimura K, Ikehara Y, Nagata T, Koide Y, Kojima N.
  • Journal Title: Procedia in Vaccinology 1 Pages: 127-134
  • 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
  • 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
  • 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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Identification of murine T-cell epitopes on low-molecular-mass secreted proteins of Mycobacterium tuberculosis. Keystone Symposia, Tuberculosis (2011)
  • 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
• [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
• [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
• [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
• [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
• [Presentation] 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): 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
• [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
  • Place of Presentation: New Orleans, LA, USA
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Characterization of murine T-cell epitopes in mycobacterial DNA-binding protein 1 (2008)
  • Author(s): Suzuki D, Nagata T, Matsumoto S, Koide Y.
  • Organizer: DNA Vaccines 2008
  • Place of Presentation: Las Vegas, NV, USA
• [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
• [Presentation] Characterization of murine T-cell epitopes in mycobacterial DNA-binding protein 1 (2008)
  • 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
• [Remarks] ホームページ
  • URL: http://www2.hama-med.ac.jp/w1c/basic/environ/Welcome.html
• [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