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，我们在自然发生的过敏性犬和实验致敏犬的体外过敏反应中检测了DNA疫苗的免疫治疗效果，并在对日本柳杉花粉敏感的特应性犬中检测了针对柳杉花粉抗原的过敏反应。大多数的狗被证明有针对Cry j1，CJ花粉的主要过敏原，IgE水平被发现在CJ的授粉季节高。接下来，CJ花粉抗原的T细胞表位从这些狗对其重叠肽的胚细胞生成反应中鉴定。在4只特应性犬中进行的Cry j1 DNA疫苗免疫治疗试验中，观察到皮内反应和外周血淋巴细胞胚细胞生成的抑制与特应性皮炎临床症状的部分改善平行，另一方面，CJ花粉提取物实验致敏的犬可诱导CJ花粉特异性气道超敏反应。在用Cry j1 DNA疫苗治疗狗后，显示出治疗组中皮内反应和气道激发中CJ花粉提取物的给药量的阈值增加，尽管治疗组和对照组之间的血清IgE水平和淋巴细胞母细胞生成反应没有差异。此外，治疗组肺内肥大细胞数量较对照组减少，提示DNA疫苗免疫治疗是一种有效的治疗变态反应性疾病的方法。

项目成果

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 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)

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.：“