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2008 Fiscal Year Annual Research Report

CD91に対する分子標的ワクチンによる結核の防御

Research Project

Project/Area Number 19659109
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

小出 幸夫  Hamamatsu University School of Medicine, 医学部, 理事 (30126809)

Co-Investigator(Kenkyū-buntansha) 永田 年  浜松医科大学, 医学部, 教授 (90275024)
内嶋 雅人  浜松医科大学, 医学部, 助教 (20252174)
瀬戸 真太郎  浜松医科大学, 医学部, 助教 (50383203)
辻村 邦夫  浜松医科大学, 医学部, 准教授 (10227407)
Keywords結核 / ワクチン / 樹状細胞 / CD91
Research Abstract

結核菌に対するワクチンとしては生菌ワクチンであるBCGが用いられているが、その成人肺結核に対する防御効果は否定的であり、より有効なワクチンの開発が急務となっている。そこで本研究では樹状細胞に選択的に抗原を取り込ませ、効率良くT細胞を感作できる分子融合蛋白ワクチンの開発を、CD91に照準を合わせて試みた。
本研究ではCD91のリガンドとして、1)結核菌由来のHeat shock protein (HSP)70と2)Thrombospondin-1(TSP-1)を利用して、結核菌抗原であるMPT51との融合蛋白をコードする遺伝子を作製した。なお、TSP-1のいくつかの機能ドメインは免疫抑制に働くことが知られているので、CD91との結合に重要であるヘパリン結合ドメインのみを使用した。次いで、作製したキメラ遺伝子を動物細胞用発現ベクターであるpCIに挿入し、マウス(BALB/cおよびC57BL/6)にDNAワクチンを施してMPT51に対する免疫応答を検討した。
HSP70/MPT51で免疫したマウスでは、MPT51単独で免疫したマウスより、CD4陽性T細胞による抗原特異的なIFN-γ産生(C57BL/6で検出)の増強が見られたが、CD8陽性T細胞によるIFN-γ産生(BALB/cで検出)の増強は認められなかった。一方、TSP-1/MPT51で免疫したマウスでは、MPT51単独で免疫したマウスと比較して、CD4陽性およびCD8陽性T細胞の両方でMPT51特異的なIFN-γ産生の強い抑制が観察された。
上記の結果から、HSP70とMPT51の融合分子による免疫により、抗原特異的なCD4陽性T細胞の免疫応答を効率よく誘導できることが明らかとなった。また、TSP-1との融合分子を用いることで、抗原特異的な免疫抑制が誘導できる可能性が示唆された。

  • Research Products

    (33 results)

All 2009 2008

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (16 results)

  • [Journal Article] The cellular niche of Listeria monocytogenes infection changes rapidly in the spleen.2009

    • Author(s)
      Taiki Aoshi, et al.
    • Journal Title

      European Journal of Immunology 39

      Pages: 417-425

    • Peer Reviewed
  • [Journal Article] Mucosal vaccine using cytotoxic T cell epitope-pulsed dendritic cell confers protection for intracelluiar pathogen.2009

    • Author(s)
      Yuichi Ozawa, et al.
    • Journal Title

      American Journal of Respiratory Cell and molecular Biology (in press)

    • Peer Reviewed
  • [Journal Article] HapMap scanning of novel human minor histocompatlbility antigens.2009

    • Author(s)
      Michi Kamei, et al.
    • Journal Title

      Blood (in press)

    • Peer Reviewed
  • [Journal Article] Effective induction of anti-tumor immune responses with oligomannosecoated liposome targeting to intraperitoneal phagocytic cells.2008

    • Author(s)
      Yuzuru Ikehara, et al.
    • Journal Title

      Cancer Letters 260

      Pages: 137-145

    • Peer Reviewed
  • [Journal Article] Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA.2008

    • Author(s)
      Takakazu Kawase, et al.
    • Journal Title

      Blood 111

      Pages: 3286-3294

    • Peer Reviewed
  • [Journal Article] The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma.2008

    • Author(s)
      Atsushi Natsume, et al.
    • Journal Title

      International Journal of Cancer 122

      Pages: 2542-2553

    • 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)
      Masayasu Hara, et al.
    • Journal Title

      Cancer Science 99

      Pages: 1471-1478

    • Peer Reviewed
  • [Journal Article] Oligomannose-coated liposomes as a therapeutic antigen-delivery and an adjuvant vehicle for induction of in vivotumor immunity.2008

    • Author(s)
      Naoya Kojima, et al.
    • Journal Title

      Journal of Control Release 129

      Pages: 26-32

    • Peer Reviewed
  • [Journal Article] Induction of regulatory dendritic cells by topical application of NF-κB decoy olieodeoxynucleotides.2008

    • Author(s)
      Iwao Isomura, et al.
    • Journal Title

      Immunology Letters 119

      Pages: 49-56

    • 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)
      Shinji Shimato, et al.
    • Journal Title

      Journal of Neurosurgery 109

      Pages: 117-122

    • 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)
      Ayako Demachi-Okamura, et al.
    • Journal Title

      Cancer Science 99

      Pages: 1633-1642

    • Peer Reviewed
  • [Journal Article] Effect of CD4^+CD25^+ regulatory T cell-depletion on acute lethal infection of mice with Trypanosoma congolense.2008

    • Author(s)
      Boniface Namangala, et al.
    • Journal Title

      Journal of Veterinary Medical Science 70

      Pages: 751-759

    • 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)
      Taiki Aoshi, et al.
    • Journal Title

      Infection and Immunity 76

      Pages: 1565-1571

    • Peer Reviewed
  • [Journal Article] Intratracheal administration of third-generation lentivirus vector encoding MPT 51 from Mycobacterium tubercell responses in the lung.2008

    • Author(s)
      Dai Hashimoto, et al.
    • Journal Title

      Vaccine 26

      Pages: 5095-5100

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

    • Author(s)
      Toshi Nagata, et al.
    • Journal Title

      Vaccine 26

      Pages: 5123-5127

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

    • Author(s)
      Masato Uchijima, et al.
    • Journal Title

      Vaccine 26

      Pages: 5165-5169

    • Peer Reviewed
  • [Journal Article] Bacterial entry to the splenic white pulp initiates antigen presentationto CD8^+ T cells.2008

    • Author(s)
      Taiki Aoshi, et al.
    • Journal Title

      Immunity 29

      Pages: 476-486

    • Peer Reviewed
  • [Presentation] Mycobacterium tuberculosis modulates the network of Rab GTPases in attenuation of phagosome maturation.2009

    • Author(s)
      Shintaro Seto, et al.
    • Organizer
      Keystone symposium
    • Place of Presentation
      Keystone
    • Year and Date
      20090100
  • [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+T細胞の解析.2009

    • Author(s)
      内嶋雅人, 他
    • Organizer
      第82回日本細菌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-13
  • [Presentation] 結核菌のHeat-shock protein 70 (HSP70)を結核菌抗原MPT51に結合させた分子融合型DNAワクチンは抗原特異的T細胞を効率良く誘導する.2009

    • Author(s)
      右藤智啓, 他
    • Organizer
      第82回日本細菌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-13
  • [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, 他
    • Organizer
      第82回日本細菌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-13
  • [Presentation] DNAワクチンを用いたMycobacterium 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, 他
    • Organizer
      第82回日本細菌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-13
  • [Presentation] 結核菌によるフアゴソーム局在性Rab GTPaseの局在変化とフアゴリソソーム形成阻害機構の解析.2009

    • Author(s)
      瀬戸真太郎, 他
    • Organizer
      第82回日本細菌学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-12
  • [Presentation] Characterization of murine T-cell epitopes on mycobacterial DNA-binding protein 1 (MDP1).2008

    • Author(s)
      Daisuke Suzuki, et al.
    • Organizer
      DNA Vaccines 200
    • Place of Presentation
      Las Vegas
    • Year and Date
      20081200
  • [Presentation] HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis using MPT51 overlappina peptides screening.2008

    • Author(s)
      Toshi Nagata, et al.
    • Organizer
      DNA Vaccines 2008
    • Place of Presentation
      Las Vegas
    • Year and Date
      20081200
  • [Presentation] Chk1 phosphorylation by Cdk1 promote mitotic entry.2008

    • Author(s)
      Masato Enomoto, et al.
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      20081200
  • [Presentation] Chkl phosphorylation by Cyclin-dependent kinase 1 promotes mitotic entry.2008

    • Author(s)
      Hidemasa Goto, et al.
    • Organizer
      48th Annual Meeting of the American Society for Cell Biology
    • Place of Presentation
      San Francisco
    • Year and Date
      20081200
  • [Presentation] 結核菌感染マクロファージにおけるRab GTPaseの網羅的局在解析.2008

    • Author(s)
      瀬戸真太郎, 他
    • Organizer
      第91回細菌学会関東支部総会
    • Place of Presentation
      千葉
    • Year and Date
      20081000
  • [Presentation] Mycobacterium tuberculosis modulates the network of Rab GTPases to inhibit phagolysosome biogenesis in macrophage.2008

    • Author(s)
      Shintaro Seto, et al.
    • 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
      20080900
  • [Presentation] Live Mycobacterium tuberculosis inhibits phagolysosome biogenesis in macrophages by modulating localization of Rab GTPase proteins on its phagosomes.2008

    • Author(s)
      Shintaro Seto, et al.
    • Organizer
      43^<rd> US-Japan conference on tuberculosis and leprosy
    • Place of Presentation
      Baltimore
    • Year and Date
      20080700
  • [Presentation] Effective induction of anti-tumor immune responses with oligomannose-coated liposomes targeting to intraperitoneal macrophages.2008

    • Author(s)
      Kunio Tsujimura, et al.
    • Organizer
      Vaccine 2nd Global Congress
    • Place of Presentation
      Boston
    • Year and Date
      2008-12-08
  • [Presentation] Genetic fusion of heat-shock protein 70 to a mycobacterial antigen enhances the antigen-specific T cell responses.2008

    • Author(s)
      右藤智啓, 他
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
  • [Presentation] Analysis of antigen-specific CD8^+ and CD4^+ T-cell responses induced by MIP-1α-MPT51 fusion DNA vaccination.2008

    • Author(s)
      Masato Uchijima, et al.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02

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Published: 2010-06-11   Modified: 2016-04-21  

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