Establishment of a novel vaccine against Mycobacterium tuberculosis employing carbohydrate-coated liposomes

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590439
• 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: TSUJIMURA Kunio Hamamatsu University School of Medicine, 医学部, 准教授 (10227407)
• Co-Investigator(Kenkyū-buntansha): KOIDE Yukio 浜松医科大学, 医学部, 理事 (30126809) ; NAGATA Toshi 浜松医科大学, 医学部, 教授 (90275024) ; UCHIJIMA Masato 浜松医科大学, 医学部, 助教 (20252174) ; SETO Shintaro 浜松医科大学, 医学部, 助教 (50383203)
• Project Period (FY): 2008 – 2010
• Keywords: ワクチン / 結核菌 / 糖鎖 / リポソーム

Research Abstract

A novel vaccine against Mycobacterium tuberculosis was established employing a tuberculosis-protective antigen MPT51 and oligomannose-coated liposomes. Antigen-specific T-cell responses and antibody production were effectively induced in mice vaccinated with this composition. In addition, induced cytokine profiles and antibody classes suggested that this newly formulated vaccine could elicit Th1-type immune responses known to be important for the protection against tuberculosis.

Research Products

• [Journal Article] Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes. (2011)
  • Author(s): 瀬戸真太郎, 辻村邦夫, 小出幸夫
  • Journal Title: Traffic 12 Pages: 407-420
  • Peer Reviewed
• [Journal Article] A novel vaccine strategy to induce mycobacterial antigen-specific Thlresponses 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] Differences in CD4^+CD25^+ regulatory T cell-depletion between Babesia microti and Babesia rodhaini infections in mice. (2010)
  • Author(s): Yokoyama N, Ikehara Y, Tiwananthagorn W, Ota N, Igarashi I, Kojima N, Taguchi O, Tsujimura K
  • Journal Title: J Protozool Res 20 Pages: 20-30
  • Peer Reviewed
• [Journal Article] Immunogenicity of dormancy-related antigens of Mycobacterium tuberculosis in DNA-vaccinated mice. (2010)
  • Author(s): Yamamura Y, Seto S, Uchijima M, Hozumi H, Nagata T, Tsujimura K, Koide Y
  • Journal Title: Procedia Vaccinology 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): 永田年, 小出幸夫
  • Journal Title: J.Biomed.Biotechnol. Pages: 764542
  • 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、小出幸夫
  • Journal Title: 日本細菌学雑誌 65 Pages: 309-324
• [Journal Article] 結核菌抗原認識とT細胞免疫 (2010)
  • Author(s): 辻村邦夫、小出幸夫
  • Journal Title: 結核 85 Pages: 509-514
• [Journal Article] Identification of murine T-cell epitopes on low-molecular-mass secreted proteins (CFP11, CFP17, and TB18.5) of Mycobacterium tuberculosis. (2010)
  • Author(s): Eweda G, Suzuki D, Nagata T, Tsuiimura K, Koide Y
  • Journal Title: Vaccine 28 Pages: 4616-4625
  • Peer Reviewed
• [Journal Article] Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phagosomes containing Mycobacterium tuberculosis in macrophages. (2010)
  • Author(s): Seto S, Matsumoto S, Tsujimura K, Koide Y
  • Journal Title: Microbiol Immunol 54 Pages: 170-174
  • Peer Reviewed
• [Journal Article] The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation. (2010)
  • Author(s): Mitsui S, Torii K, Fukui H, Tsujimura K, Maeda A, Nose M, Nagatsu A, Mizukami H, Morita A
  • Journal Title: J Pharmacol Exp Ther 333 Pages: 954-960
  • Peer Reviewed
• [Journal Article] Identification of HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secretory protein derived from Mycobacterium tuberculosis using MPT51 overlapping peptides screening and DNA vaccination. (2010)
  • Author(s): Wang L-X, Nagata T, Tsujimura K, Uchiiima M, Seto S, Koide Y
  • Journal Title: Vaccine 28 Pages: 2026-2031
  • Peer Reviewed
• [Journal Article] Characterization of murine T-cell epitopes on mycobacterial DNA-binding protein 1 (MDPI) 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
  • Peer Reviewed
• [Journal Article] Etanercept treatment reduces the serum levels of interleukin- 15 and interferon-gamma inducible protein-10 in patients with rheumatoid arthritis. (2010)
  • Author(s): Ichikawa T, Kageyama Y, Kobayashi H, Kato N, Tsujimura K, Koide Y
  • Journal Title: Rheumatol Int 30 Pages: 725-730
  • Peer Reviewed
• [Journal Article] A novel positive feedback loop between Cyclin-dependent kinase 1 (CDK1) and CHKI in the nucleus during the G2/M transition. (2009)
  • Author(s): Enomoto M, Goto H, Tomono Y, Kasahara K, Tsujimura K, Kiyono T, Inagaki M
  • Journal Title: J Biol Chem 284 Pages: 34223-34230
  • Peer Reviewed
• [Journal Article] Induction of anti-tumor immune 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 Vaccinology 1 Pages: 127-134
  • Peer Reviewed
• [Journal Article] Dissection of Rab7 localization on Mycobacterium tuberculosis phagosome. (2009)
  • Author(s): Seto S, Matsumoto S, Ohta I, Tsujimura K, Koide Y
  • Journal Title: Biochem Biophys Res Common 387 Pages: 272-277
  • Peer Reviewed
• [Journal Article] Mucosal vaccine using CTL epitope-pulsed dendritic cell confers protection for intracellular pathogen. (2009)
  • Author(s): Ozawa Y, Suda T, Hashimoto D, Hashimoto D, Nakamura Y, Enomoto N, Inui N, Koide Y, Nakamura H, Chida K.
  • Journal Title: Am J Respir Cell Mol Bird 41 Pages: 440-448
  • Peer Reviewed
• [Journal Article] HapMap scanning of novel human minor histocompatibility antigens. (2009)
  • Author(s): Kamei M, Nannya Y, Torikai H, Kawase T, Taura K, Inamoto Y, Takahashi T, Yazaki M, Morishima S, Tsuiimura K, Miyamura K, Ito T, Togari H, Riddell SR, Kodera Y, Morishima Y, Takahashi T, Kuzushima K, Ogawa S, Akatsuka Y
  • Journal Title: Blood 113 Pages: 5041-5048
  • Peer Reviewed
• [Journal Article] The cellular niche of Lesteria monocytogenes infection changes rapidly in the spleen. (2009)
  • Author(s): Aoshi T, Carrero JA, Konjufca V, Koide Y, Unanue ER, Miller MJ
  • Journal Title: Ear J Immunol 39 Pages: 417-425
  • Peer Reviewed
• [Journal Article] Bacterial entry to the splenic white pulp initiates antigen presentation to CD8^+ T cells. (2008)
  • Author(s): Aoshi T, Zinselmeyer BH, Konjufca V, Lynch JN, Zhang X, Koide Y, Miller MJ
  • Journal Title: Immunity 29 Pages: 476-486
  • Peer Reviewed
• [Journal Article] Chemokine receptor-mediated delivery of mycobacterial MPT51 protein efficiently induces antigen-specific T-cell responses. (2008)
  • Author(s): Uchiiima M, Nagata T, Koide Y
  • Journal Title: Vaccine 26 Pages: 5165-5169
  • 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, Uchiiima M, Koide Y
  • Journal Title: Vaccine 26 Pages: 5123-5127
  • 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, Suda T, Chida K, Miyoshi H, Nakamura H, Koide Y
  • Journal Title: Vaccine 26 Pages: 5095-5100
  • Peer Reviewed
• [Journal Article] Identification of an 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, Uchiiima M, Hashimoto D, Rafiei A, Suda T, Chida K, Koide Y
  • Journal Title: Infect human 76 Pages: 1565-1571
  • Peer Reviewed
• [Journal Article] Effect of CD4^+CD25^+ regulatory T cell-depletion on acute lethal infection of mice with Trypanosoma congolense. (2008)
  • Author(s): Namangala B, Yokoyama N, Ikehara Y, Taguchi O, Tsujimura K, Sugimoto C, Inoue N
  • Journal Title: J Vet Med Sci 70 Pages: 751-759
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear antigen 1-specific CD4^+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells. (2008)
  • Author(s): Demachi-Okamura A, Ito Y, Akatsuka Y, Tsujimura K, Morishima Y, Takahashi T, Kuzushima K
  • Journal Title: Cancer Sci 99 Pages: 1633-1642
  • Peer Reviewed
• [Journal Article] Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen. (2008)
  • Author(s): Shimato S, Natsume A, Wakabayashi T, Tsujimura K, Nakahara N, Ishii J, Ito M, Akatsuka Y, Kuzushima K, Yoshida J
  • Journal Title: J Neurosurg 109 Pages: 117-122
  • Peer Reviewed
• [Journal Article] Induction of regulatory dendritic cells by topical application of NF-KB decoy oligodeoxynucleotides. (2008)
  • Author(s): Isomura I Shintani Y, Yasuda Y, Tsujimura K, Morita A
  • Journal Title: Immunol Lett 119 Pages: 49-56
  • Peer Reviewed
• [Journal Article] Oligomannose-coated liposomes as a therapeutic antigen-delivery and an adjuvant vehicle for induction of in vivo tumor immunity. (2008)
  • Author(s): Kojima N, Biao L, Nakayama T, Ishii M, Ikehara Y, Tsujimura K
  • Journal Title: J Control Release 129 Pages: 26-32
  • Peer Reviewed
• [Journal Article] Interleukin-2 potentiation of cetuximab antitumor activity for epidermal growth factor receptor-overexpressing gastric cancer xenografts through antibody-dependent cellular cytotoxicity. (2008)
  • Author(s): Ham M, Nakanishi H, Tsujimura K, Matsui M, Yatabe Y, Manabe T, Tatematsu M
  • Journal Title: Cancer Sci 99 Pages: 1471-1478
  • Peer Reviewed
• [Journal Article] The DNA demethylating agent 5-aza-2'- deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. (2008)
  • Author(s): Natsume A, Wakabayashi T, Tsujimura K, Shimato S, Ito M, Kuzushima K, Kondo Y, Sekido Y, Kawatsura H, Narita Y, Yoshida J
  • Journal Title: Int J Cancer 122 Pages: 2542-2553
  • Peer Reviewed
• [Journal Article] Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. (2008)
  • Author(s): Kawase T, Nanya Y, Torikai H, Yamamoto G, Onizuka M, Morishima S, Tsujimura K, Miyamura K, Kodera Y, Morishima Y, Takahashi T, Kuzushima K, Ogawa S, Akatsuka Y
  • Journal Title: Blood 111 Pages: 3286-3294
  • Peer Reviewed
• [Journal Article] Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells (2008)
  • Author(s): Ikehara Y, Shiuchi N, Kabata-Ikehara S, Nakanishi H, Yokoyama N, Takagi H, Nagata T, Koide Y, Kuzushima K, Takahashi T, Tsujimura K, Kojima N
  • Journal Title: Cancer Lett 260 Pages: 137-145
  • Peer Reviewed
• [Journal Article] 結核菌ファゴソームの成熟阻害機構
  • Author(s): 瀬戸真太郎、辻村邦夫、小出幸夫
  • Journal Title: 化学療法の領域 印刷中
• [Journal Article] 結核菌の細胞内寄生メカニズム
  • Author(s): 瀬戸真太郎、辻村邦夫、小出幸夫
  • Journal Title: 日本臨床 印刷中
• [Presentation] Immunogenicity of latency-associated antigens of Mycobacterium tuberculosis in DNA-vaccinated mice. (2010)
  • Author(s): Tsuiimura K, Yamamura Y, Hozumi H, Seto S, Uchijima M, Koide Y
  • Organizer: The 10th Kyungpook-Hamamatsu Joint Medical Symposium.
  • Place of Presentation: 浜松
  • Year and Date: 20100000
• [Presentation] Proteomic analysis revealed the interaction of endoplasmic reticulum with the phagosomes containing Mycobacterium tuberculosis in macrophages. (2010)
  • Author(s): Seto S, Tsuiimura K, Koide Y
  • Organizer: The 10th Kyungpook-Hamamatsu Joint Medical Symposium.
  • Place of Presentation: 浜松
  • Year and Date: 20100000
• [Presentation] Immune responses against dormancy-associated antigens of Mycobacterium tuberculosis in DNA-vaccinated mice. (2010)
  • Author(s): Yamamura Y, Seto S, Uchijima M, Tsuiimura K, Koide Y
  • Organizer: 45th US-Japan Conference on Tuberculosis and Leprosy.
  • Place of Presentation: Cambridge/USA
  • Year and Date: 20100000
• [Presentation] Proteomic analysis reveals the interaction of endoplasmic reticulum with the phagosome containing Mycobacterium tuberculosis. (2010)
  • Author(s): Koide Y, Seto S, Tsujimura K
  • Organizer: 45th US-Japan Conference on Tuberculosis and Leprosy.
  • Place of Presentation: Cambridge/USA
  • Year and Date: 20100000
• [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 vaccine 2010.
  • Place of Presentation: New Orleans/USA
  • Year and Date: 20100000
• [Presentation] Immunogenicity of dormancy-related antigens of Mycobacterium tuberculosis in DNA-vaccinated mice. (2010)
  • Author(s): Yamamura Y, Seto S, Uchijima M, Hodumi H, Nagata T, Tsuiimura K, Koide Y
  • Organizer: DNA vaccine 2010.
  • Place of Presentation: New Orleans/USA
  • Year and Date: 20100000
• [Presentation] Genetic fusion of heat-shock protein 70 to a mycobacterial antigen enhances the antigen-specific T cell responses. (2009)
  • Author(s): Uto T, Uchijima M, Seto S, Nagata T, Suda T, Chida K, Nakamura H, Tsuiimura K, Koide Y
  • Organizer: Vaccine 3rd Global Congress.
  • Place of Presentation: Singapore/Republic of Singapore
  • Year and Date: 20090000
• [Presentation] Alternative localization of Rab GTPases to phagosome containing Mycobacterium tuberculosis in inhibition of phagolysosome biogenesis. (2009)
  • Author(s): Seto S, Koide Y
  • Organizer: 44th US-Japan Conference on Tuberculosis and Leprosy.
  • Place of Presentation: 福岡
  • Year and Date: 20090000
• [Presentation] Cancer vaccine delivery using oligomannose coated liposomes. (2009)
  • Author(s): Ikehara Y, Ikehara SK, Yokoyama N, Kuzushima K, Takahashi T, Kojima N, Tsuiimura K
  • Organizer: AACR 100th Annual Meeting.
  • Year and Date: 20090000
• [Presentation] Mycobacterium tuberculosis modulates the network of Rab GTPases in attenuation of phagosome maturation. (2009)
  • Author(s): Seto S, Koide Y
  • Organizer: Keystone symposium.
  • Place of Presentation: Keystone/USA
  • Year and Date: 20090000
• [Presentation] Chk1 phosphorylation by Cyclin-dependent kinase 1 promotes mitotic entry. (2008)
  • Author(s): Goto H, Enomoto M, Tomono Y, Kasahara K, Ikegami Y, Tsuiimura K, Kiyono T, Inagaki M
  • Organizer: 48th Annual Meeting of the American Society for Cell Biology.
  • Place of Presentation: San Francisco/USA
  • Year and Date: 20080000
• [Presentation] Identification of HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis using MPT51 overlapping peptides screening. (2008)
  • Author(s): Nagata T, Wang L-X, Koide Y
  • Organizer: DNA Vaccines 2008
  • Place of Presentation: Las Vegas/USA
  • Year and Date: 20080000
• [Presentation] Characterization of routine T-cell epitopes on mycobacterial DNA-binding protein 1(MDPI). (2008)
  • Author(s): Suzuki D, Nagata T, Matsumoto S, Koide Y
  • Organizer: DNA Vaccines 2008
  • Place of Presentation: Las Vegas/USA
  • Year and Date: 20080000
• [Presentation] Effective induction of anti-tumor immune responses with oligomannose-coated liposomes targeting to intraperitoneal macrophages. (2008)
  • Author(s): Tsuiimura K, Ikehara Y, Nagata T, Koide Y, Kojima N
  • Organizer: Vaccine 2nd Global Congress.
  • Place of Presentation: Boston/USA
  • Year and Date: 20080000
• [Presentation] Mycobacterium tuberculosis modulates the network of Rab GTPases to inhibit phagolysosome biogenesis in macrophage. (2008)
  • Author(s): Seto S, Koide Y
  • Organizer: 第8回あわじ感染症・免疫フォーラム.
  • Place of Presentation: 淡路
  • Year and Date: 20080000
• [Presentation] Live Mycobacterium tuberculosis inhibits phagolysosome biogenesis in macrophages by modulating localization of Rab GTPase proteins on its phagosomes. (2008)
  • Author(s): Seto S, Koide Y
  • Organizer: 43rd US-Japan conference on tuberculosis and leprosy.
  • Place of Presentation: Baltimore/USA
  • Year and Date: 20080000
• [Presentation] The DNA demethylating agent 5-aza-2'- deoxycytidine induces the expression of cancer-testis antigens in human gliomas : epigenetic target for tumor immunotherapy. (2008)
  • Author(s): Natsume A, Wakabayashi T, Shimato S, Tsujimura K, Kuzushima K, Yoshida J
  • Organizer: The 17th International Conference on Brain Tumor Research and Therapy.
  • Place of Presentation: 函館
  • Year and Date: 20080000
• [Book] Handbook of Listeria monocytogenes.(Chapter 15.Anti-infective vaccine strategies.) (2008)
  • Author(s): Nagata T, Koide Y
  • Total Pages: 449-480
  • Publisher: CRC Press.
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] Liposome composition fbr immune induction (2009)
  • Inventor(s): Kojima N, Ikehara Y, Tsujimura K
  • Industrial Property Rights Holder: Tokai University Educational system, Aichi Prefecture
  • Industrial Property Number: 特許,11/909,912(PCT/7P2006/306483)
  • Filing Date: 2009-05-29
• [Patent(Industrial Property Rights)] Liposome composition for immune induction (2009)
  • Inventor(s): Kojima N, Ikehara Y, Tsujimura K
  • Industrial Property Rights Holder: Tokai University Educational system, Aichi Prefecture
  • Industrial Property Number: 特許,EAOl2618(PCT/7P2006/306483)
  • Filing Date: 2009-10-30
• [Patent(Industrial Property Rights)] Liposome composition for immune induction (2008)
  • Inventor(s): Kojima N, Ikehara Y, Tsujimura K
  • Industrial Property Rights Holder: Tokai University Educational system, Aichi Prefecture
  • Industrial Property Number: 特許,CA 2634038(PCT/JP2006/306483)
  • Filing Date: 2008-06-12