Development of DNA vaccine therapy for allergic diseases in animals

动物过敏性疾病DNA疫苗疗法的开发

• 批准号: 12556056
• 负责人: TSUJIMOTO Hajime
• 金额: $ 8万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12556056/
• 关键词: 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

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.

为了建立一种有效的DNA疫苗免疫治疗过敏性疾病的方法，我们检测了自发性过敏犬和实验性致敏犬的体外过敏反应，并探讨了DNA疫苗免疫治疗的体内效果。CJ花粉的主要过敏原Cry J1的IgE水平在CJ花粉授粉季节较高。接下来，从CJ花粉抗原的重叠多肽在这些狗身上的始发反应中鉴定出CJ花粉抗原的T细胞表位。在用Cry J1 DNA疫苗对4只特应性狗进行的实验性免疫治疗试验中，观察到在特应性皮炎临床症状部分改善的同时，Cry J1 DNA疫苗对皮肤内反应和外周血淋巴细胞的转化也有抑制作用。另一方面，CJ花粉提取物可以在实验致敏的狗身上诱导出CJ花粉特异性的呼吸道超敏反应。用Cry J1 DNA疫苗治疗犬后，虽然血清IgE水平和淋巴细胞转化反应与对照组无明显差异，但治疗组皮内反应和呼吸道刺激的CJ花粉提取液量阈值均有提高。此外，与对照组相比，治疗组肺内肥大细胞的数量较少。本研究为DNA疫苗免疫治疗变态反应性疾病提供了证据。

项目成果

Masuda K., et al.: "In vivo and in vitro tests showing sensitization to Japanese cedar (Cryptomeria japonica) pollen allergen in atopic dogs."J.Vet.Med.Sci.. 62. 995-1000 (2000)

Masuda K. 等人：“体内和体外测试显示特应性狗对日本柳杉 (Cryptomeria japonica) 花粉过敏原过敏。”J.Vet.Med.Sci.. 62. 995-1000 (2000)

Sakaguchi, M., et al.: "Analysis of canine IgE-binding epitope on the major allergen(Cry j 1)of Japanese cedar pollen with anti-Cry j 1 monoclonal antibodies"Vet.Immunol.Immunopathol.. 78. 35-43 (2001)

Sakaguchi, M., 等人：“用抗 Cry j 1 单克隆抗体分析日本柳杉花粉主要过敏原 (Cry j 1) 上的犬 IgE 结合表位”Vet.Immunol.Immunopathol.. 78. 35-

Masuda, K., et al.: "In vivo and in vitro tests showing sensitization to Japanese cedar (Cryptomeria japonica)pollen in atopic dogs"J.Vet.Med.Sci.. 62. 995-1000 (2000)

Masuda, K., et al.：“体内和体外测试显示特应性狗对日本柳杉 (Cryptomeria japonica) 花粉的敏感性”J.Vet.Med.Sci.. 62. 995-1000 (2000)

Masuda, K., et al.: "Seasonal rhinitis in a cat sensitized to Japanese cedar(Cryptomeria japonica)pollen"J.Vet.Med.Sci.. 63. 79-81 (2001)

Masuda, K., et al.：“对日本柳杉（Cryptomeria japonica）花粉敏感的猫的季节性鼻炎”J.Vet.Med.Sci.. 63. 79-81 (2001)

Masuda, K., Sakaguchi, M., Saiio, S., DeBoer, D.J., Fujiwara, S., Kurata, K., Yamashita, K., Hasegawa, A., Ohno, K., Tsujimoto, H.: "In vivo and in vitro tests showing sensitization to Japanese cedar (Cryptomeria japonica) pollen in atopic dogs."J.Vel.Med

Masuda, K.、Sakaguchi, M.、Saiio, S.、DeBoer, D.J.、Fujiwara, S.、Kurata, K.、Yamashita, K.、Hasekawa, A.、Ohno, K.、Tsujimoto, H.：“