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2005 Fiscal Year Final Research Report Summary

Development of T cell vaccination strategies against experimental Changas' disease.

Research Project

Project/Area Number 16590346
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionJuntendo University

Principal Investigator

MIYAHIRA Yasushi  Juntendo University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究科, 講師 (40265781)

Project Period (FY) 2004 – 2005
KeywordsCD8^+T cells / Trypanosoma cruzi / Recombinant adenovirus / Recombinant vaccinia virus / Adjuvant / Infection control strategies / T cell vaccine / Experimental Chagas' diseases
Research Abstract

After having completed our 2-year research activities, we established the following findings.
(1) We have generated two recombinant viruses, recombinant adenovirus and recombinant vaccinia virus, which were inserted with a gene encoding the H-2^b-restricted CD8^+ T cell epitope (ANYNFTLV) identified on Trypanosoma cruzi trans-sialidase surface antigen (TSSA).
(2) We have demonstrated the immunogenicity of both recombinant viruses by detecting ANYNFTLV-specific CD8^+ T cells in splenocytes derived from virus-immunized B6 mice. However, the immunogenicity of both recombinant viruses was markedly different with regard to the level of CD8^+ T cell induction. Recombinant adenovirus was more efficient for priming the CD8^+ T cell responses.
(3) By performing the prime/boost immunization using TSSA-encoding DNA vaccine, recombinant adenovirus and recombinant vaccinia virus, we have demonstrated that the recombinant vaccinia virus was the best to exhibit maximal boosting capacity for the inductio … More n of ANYNFTLV-specific CD8^+ T cell responses.
(4) By increasing the immunizing doses of both recombinant viruses for prime/boost to 5 x 10^8 per head, the induction of ANYNFTLV-specific CD8^+ T cells has become better than the one induced by 5 x 10^7 per head-immunization.
(5) Considering that the RANKL (Ligand to receptor activator of NFκB) gene was effective as a genetic adjuvant for enhancing antigen-specific CD8^+ T cell responses, we have generated murine RANKL-expressing recombinant vaccinia virus. By coadministrating the RANKL-expressing recombinant vaccinia virus with ANYNFTLV-expressing recombinant viruses, we have demonstrated the enhanced induction of antigen-specific CD8^+ T cells.
(6) Mice immunized with ANYNFTLV-expressing recombinant viruses for prime/boost with RANKL-expressing recombinant vaccinia virus were completely protected from the lethal T.cruzi infection. We have demonstrated, for the first time that the immune responses against a single CD8^+ T cell epitope induced by virus vector vaccination was sufficient to confer protective immunity in experimental Chagas' disease.
These results have clarified, at least partly, the optimal T cell vaccination strategy against intracellular infectious agents. Our efforts for defining effective T cell vaccines against intracellular infectious agent(s) will be continued further based on our findings presented above. Less

  • Research Products

    (14 results)

All 2005 2004

All Journal Article (10 results) Book (4 results)

  • [Journal Article] Immune responses against a single CD8~+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection2005

    • Author(s)
      Miyahira Y., et al.
    • Journal Title

      Infection and Immunity 73(11)

      Pages: 7356-7365

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] SCCA2-transfected human keratinocytes show increased secretion of IL-1α and IL-6,but not of TNF-α2005

    • Author(s)
      Titapowatanakun B., Miyahira Y., et al.
    • Journal Title

      Archives of Dermatological Research 297(6)

      Pages: 274-277

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 免疫と疾患(前編)-自然・獲得免疫と疾患- 「寄生原虫感染症」2005

    • Author(s)
      宮平 靖
    • Journal Title

      最新医学(宮坂信之編) 60

      Pages: 736-748

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TNFファミリー蛋白遺伝子のアジュバント効果-ワクチンの免疫効果の増強法と誘導免疫の特性-2005

    • Author(s)
      宮平 靖
    • Journal Title

      臨床免疫 43

      Pages: 628-634

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immune responses against a single CD8^+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection2005

    • Author(s)
      Miyahira Y., et al.
    • Journal Title

      Infection and Immunity 73(11)

      Pages: 7356-7365

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] SCCA2-transfected human keratinocytes show increased secretion of IL-1α and IL-6,but not of TNF-α2005

    • Author(s)
      Titapiwatanakun B., Miyahira Y., et al.
    • Journal Title

      Archives of Dermatological Research 297(6)

      Pages: 274-277

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Diseases and innate/acquired immunity (in Japanese)2005

    • Author(s)
      Miyahira Y.
    • Journal Title

      Saishin-Igaku 60

      Pages: 736-748

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A potent adjuvant effect of NFκB gene (in Japanese)2005

    • Author(s)
      Miyahira Y.
    • Journal Title

      Rinsho-Men-eki 43

      Pages: 628-634

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 細胞内寄生虫感染症に対するT細胞ワクチン手法の開発-細胞内寄生虫感染症をモデルとして-2004

    • Author(s)
      宮平 靖
    • Journal Title

      慶應医学 81

      Pages: 207-220

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Development of T cell vaccination strategies against intracellular infectious agents-Analyses of parasitic protozoa infections- (in Japanese)2004

    • Author(s)
      Miyahira Y.
    • Journal Title

      Keio-Igaku 81

      Pages: 207-220

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 国際保険・看護(丸井 英二, 森口 育子 編)「マラリア」2005

    • Author(s)
      宮平 靖
    • Total Pages
      57-64
    • Publisher
      弘文堂
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Malaria In "International Health and Nursing" (eds. Eiji Marui and Ikuko Moriguchi)2005

    • Author(s)
      Miyahira Y.
    • Total Pages
      57-64
    • Publisher
      Ko-Bun-Do, Tokyo, Japan (in Japanese)
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 「寄生虫感染症に対する免疫反応」2004

    • Author(s)
      宮平 靖
    • Total Pages
      183-191
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Immune responses against parasitic protozoa infections In "Annual Review Immunology 2005" (eds. Ko Okumura, Toshio Hirano, Noriyuki Sato)2004

    • Author(s)
      Miyahira Y.
    • Total Pages
      183-191
    • Publisher
      Chu-Gai-Igaku, Tokyo Japan (in Japanese)
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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