| Project/Area Number |
12556056
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Applied veterinary science
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
TSUJIMOTO Hajime The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (60163804)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAGUCHI Masahiro National Institute of Infectious, Division of Immunology, A chief researcher, 免疫部, 主任研究官 (20170590)
MASUDA Kenichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, assistant, 大学院・農学生命科学研究科, 助手 (40313077)
OHNO Koichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (90294660)
HIRAHARA Kazuki Sankyo Pharmaceutical, Third Institute of Biology, researcher, 第三生物研究所, 研究職
佐々木 伸雄 東京大学, 大学院・農学生命科学研究科, 教授 (60107414)
白石 明郎 三共株式会社, 第3生物研究所, 所次長(研究職)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2001: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2000: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Dog / DNA vaccine / Cry j1 / T-cell epitope / Atopic dermatitis / 腫瘍マーカー / テロメア / テロメラーゼ / 薬剤耐性 / p53 / MDM2 / 猫白血病ウイルス(FeLV) / クローナリティー / P糖蛋白質 / アレルギー性疾患 / 日本スギ花粉 / ハウスダストマイト / ペプチド療法 / 実験感作犬 |
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| Research Abstract |
In order to establish an effective immunotherapy for allergic diseases using DNA vaccine, we examined the in vitro allergic reactions in spontaneously occurring allergic dogs and experimentally sensitized dogs and then explored in vivo efficacy of the immunotherapy using DNA vaccine.
Allergic reactions directed to Japanese cedar (Cryptomeria japonica, CJ) pollen antigens were examined in atopic dogs sensitive to CJ pollen. Most of the dogs were shown to have IgE directed to Cry j1, a major allergen of CJ pollen, and the IgE level was found to be high in the pollenation season of CJ. Next, T-cell epitopes of CJ pollen antigen were identified from the blastogenesis response to its overlapping peptides in these dogs. In an experimental immunotherapy trial using Cry j1 DNA vaccine in 4 atopic dogs, suppression of intradermal reaction and blastogenesis of peripheral blood lymphocytes was observed in parallel to the partial improvement of the clinical sings of atopic dermatitis.
On the other hand, CJ pollen-specific airway hypersensitivity could be induced in dogs experimentally sensitized with CJ pollen extract. After treatment of the dogs with Cry j1 DNA vaccine, threshold of the administered amount of CJ pollen extract in the intradermal reaction and airway provocation was shown to be increased in the treatment group, although the serum IgE level and lymphocyte blastogenesis response were not different between the treatment and control groups. Furthermore, the number of mast cells in the lung was smaller in the treatment group in comparison to the control group.
The present study provided evidence to indicate that DNA vaccine immunotherapy can be considered as an effective therapy for allergic diseases.
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