Development of a new class of lipid-based vaccines against tuberculosis

• Project/Area Number: 18390289
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyoto University
• Principal Investigator: SUGITA Masahiko Kyoto University, ウイルス研究所, 教授 (80333532)
• Co-Investigator(Kenkyū-buntansha): MATSUNAGA Isamu 京都大学, ウイルス研究所, 助教 (00254425) ; 廣松 賢治 福岡大学, 医学部, 教授 (80252237)
• Co-Investigator(Renkei-kenkyūsha): HIROMATSU Kenji 福岡大学, 医学部医学部, 教授 (80252237)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,700,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2006: ¥6,000,000 (Direct Cost: ¥6,000,000)
• Keywords: 感染症学 / 結核 / 脂質 / ワクチン / 細菌 / 感染症 / 免疫学

Research Abstract

結核の再興が社会問題化し、現行のBCGワクチンに替わる新しい抗結核ワクチンの開発が望まれている。本課題においては、結核菌脂質に対する新しい免疫応答に着目し、その全容の解明と賦活法の確立を通して、脂質をベースにした新たな抗結核ワクチンを開発することを目的として研究を展開した。その結果、結核菌が産生する糖脂質の新たな生合成経路を発見し、それに対する免疫応答を実証することにより、有望な抗結核脂質ワクチンの候補が絞られた。

Research Products

• [Journal Article] Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation(USA) (2008)
  • Author(s): Hava DL, van der Wel N, Cohen N, Dascher CC, Houben D, Leon L, Agarwal S, Sugita M, van Zon M, Kent SC, Shams H, Peters PJ, Brenner MB
  • Journal Title: Proc. Natl. Acad. Sci 105 Pages: 11281-11286
  • Peer Reviewed
• [Journal Article] Mycolyltransferase-mediated glycolipid exchange in mycobacteria (2008)
  • Author(s): Matsunaga I, Naka T, Talekar RS, McConnell MJ, Katoh K, Nakao H, Otsuka A, Behar SM, Yano I, Moody DB, Sugita M
  • Journal Title: J. Biol. Chem 283 Pages: 28835-28841
  • Peer Reviewed
• [Journal Article] Identification of antibody responses to the serotype-nonspecific molecular species of glycopeptidolipids in Mycobacterium avium infection (2008)
  • Author(s): Matsunaga I, Komori T, Ochi A, Mori N, Sugita M
  • Journal Title: Biochem. Biophys. Res. Commun 377 Pages: 165-169
  • Peer Reviewed
• [Journal Article] Trans-species activation of human T cells by rhesus macaque CD1b molecules (2008)
  • Author(s): Morita D, Katoh K, Harada T, Nakagawa Y, Matsunaga I, Miura T, Adachi A, Igarashi T, Sugita M
  • Journal Title: Biochem. Biophys. Res. Commun 377 Pages: 889-893
  • Peer Reviewed
• [Journal Article] Trehalose dimycolate elicits eosinophilic skin hypersensitivity in mycobacteria-infected guinea pigs (2008)
  • Author(s): Otsuka A, Matsunaga I, Komori T, Tomita K, Toda Y, Manabe T, Miyachi Y, Sugita M
  • Journal Title: J. Immunol 181 Pages: 8528-8533
  • Peer Reviewed
• [Journal Article] Mycolyltransferase-mediated glycolipid exchange in mycobacteria. (2008)
  • Author(s): Matsunaga I, et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 28835-28841
  • Peer Reviewed
• [Journal Article] Trans-species activation of human T cells by rhesus macaque CDlb molecules. (2008)
  • Author(s): Morita D, et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 377 Pages: 889-893
  • Peer Reviewed
• [Journal Article] Lipid-specific immune responses against tuberculosis ; from basic science to medical applications. Curr (2007)
  • Author(s): Matsunaga I, Sugita M
  • Journal Title: Immunol. Rev 3 Pages: 145-150
  • Peer Reviewed
• [Journal Article] Pathways of CD1 and lipid antigen delivery, trafficking, processing, loading and presentation (2007)
  • Author(s): Sugita M, Barral DC, Brenner MB
  • Journal Title: Curr. Top. Microbiol. Immunol 314 Pages: 143-164
  • Peer Reviewed
• [Journal Article] Pathways of CD1 and lipid antigen delivery, trafficking, processing, loading and presentation. (2007)
  • Author(s): Sugita M, Barral DC, Brenner MB.
  • Journal Title: Current Topics in Microbiology and Immunology 314 Pages: 143-164
  • Peer Reviewed
• [Journal Article] Lipid-specific immune responses against tuberculosis: from basic science to medical applications. (2007)
  • Author(s): Matsunaga I, Sugita M.
  • Journal Title: Current Immunology Reviews 3 Pages: 145-150
  • Peer Reviewed
• [Journal Article] Pathways of CD1 and lipid antigen delivery, trafficking, processing, loading and presentation. (2007)
  • Author(s): Sugita M, Barral DC, Brenner MB
  • Journal Title: Current Topics in Microbiology and Immunology (印刷中)
• [Journal Article] 結核菌脂質成分に対する免疫応答の分子機序 (2006)
  • Author(s): 杉田昌彦
  • Journal Title: 日本細菌学雑誌 61巻 Pages: 405-413
  • NAID: 10018643592
• [Journal Article] BCG vaccine elicits both T-cell mediated and humoral immune responses directed against mycobacterial lipid components. (2006)
  • Author(s): Watanabe Y 他10名
  • Journal Title: Vaccine 24・29-30 Pages: 5700-5707
• [Presentation] ミコール酸転移酵素による脂質T細胞抗原の生合成 (2008)
  • Author(s): 松永勇、中崇、加藤久美子、中尾瞳、大塚篤司、矢野郁也、杉田昌彦
  • Organizer: 第81回日本生化学会総会
  • Place of Presentation: 神戸
• [Presentation] Eosinophilic skin reactions to glycolipids define a novel form of hypersensitivity in mycobacterial infection (2008)
  • Author(s): Otsuka A, Matsunaga I, Miyachi Y, Sugita M
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
• [Presentation] Eosinophilic skin reactions to glycolipids in mycobacterial infection represent a novel form of delayed-type hypersensitivity (2008)
  • Author(s): Otsuka A, Matsunaga I, Komori T, Tomita K, Toda Y, Manabe T, Miyachi Y, Sugita M
  • Organizer: The International Investigative Dermatology 2008
  • Place of Presentation: Kyoto
• [Presentation] 感染防御と脂質免疫 (2007)
  • Author(s): 杉田昌彦
  • Organizer: 第81回日本感染症学会教育講演
  • Place of Presentation: 京都
  • Year and Date: 2007-04-10