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.

为了使用DNA疫苗为过敏性疾病建立有效的免疫疗法，我们检查了自发发生的过敏犬和实验敏化的狗的体外过敏反应，然后在体内探索了使用DNA疫苗的体内功效。对CJ花粉敏感。大多数狗都被证明是指CRY J1（CJ粉的主要过敏原），在CJ的粉季季节中发现IgE水平很高。接下来，从对其对这些狗中的重叠肽的囊泡反应中鉴定出CJ花粉抗原的T细胞表位。在一项实验性免疫疗法试验中，使用CRY J1 DNA疫苗在4种特应犬中，抑制皮内反应和外周血血液淋巴细胞的囊性与部分改善特征性皮肤炎的临床作用并平行于外周血液淋巴细胞的散发性。在另一只手的临床疾病中，CJ粉传播的狗可以施加刺激性刺激性。用CRY J1 DNA疫苗治疗狗后，在治疗组中，在皮内反应和气道挑衅中施用的CJ花粉提取物的阈值被证明增加了，尽管治疗组和对照组之间的血清IGE水平和淋巴细胞爆炸反应并没有差异。此外，与对照组相比，治疗组中肺中的肥大细胞数量较小。目前的研究提供了证据表明DNA疫苗免疫疗法可以被视为对过敏性疾病的有效疗法。

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)

Masuda, K., Sakaguchi, M., Saito, S., DeBoer, D.J., Yamashita, K., Hasegawa, A., Ohno, K., Tsujimoto, H.: "Seasonal atopic dermatitis in dogs sensitive to a major allergen of Japanese cedar (Cryptomeria japonica) pollen."Vet.Dermatol.. 13. 53-59 (2002)

Masuda, K.、Sakaguchi, M.、Saito, S.、DeBoer, D.J.、Yamashita, K.、Hasekawa, A.、Ohno, K.、Tsujimoto, H.：“对主要过敏原敏感的狗的季节性特应性皮炎

Masuda K., et al.: "Positive reactions to common allergens in 42 atopic dogs in Japan"Vet.Immunol.Immunopathol.. 73. 193-204 (2000)

Masuda K., et al.：“日本 42 只特应性狗对常见过敏原的阳性反应”Vet.Immunol.Immunopathol.. 73. 193-204 (2000)

Sakaguchi, M., Masuda, K., Toda, M., Inouye, S., Yasueda, H., Taniguchi, Y., Nagoya, T., DeBoer, D.J., Tsujimoto, H.: "Analysis of canine IgE-binding epitope on the major allergen (Cry j 1) of Japanese cedar pollen with anti-Cry j1 monoclonal antibodies."

Sakaguchi, M.、Masuda, K.、Toda, M.、Inouye, S.、Yasueda, H.、Taniguchi, Y.、Nagoya, T.、DeBoer, D.J.、Tsujimoto, H.：“犬 IgE 分析

Masuda, K., Kurata, K., Sakaguchi, M., Yamashita, K., Hasegawa, A., Ohno, K., Tsujimoto, H.: "Seasonal rhinitis in a cat sensitized to Japanese cedar (Cryptomeria japonica) pollen."J.Vet.Med.Sci.. 63. 79-81 (2001)

Masuda, K.、Kurata, K.、Sakaguchi, M.、Yamashita, K.、Hasekawa, A.、Ohno, K.、Tsujimoto, H.：“对日本雪松（Cryptomeria japonica）花粉敏感的猫的季节性鼻炎