在我国过敏性疾病患者达2亿多人，尘螨是最主要的过敏原（阳性率>70%）。WHO公认过敏性疾病变应原免疫治疗（脱敏治疗）是唯一对因治疗的方法。但现有尘螨疫苗仍有许多不足，如含大量杂蛋白和易引发过敏反应、长期反复注射依从性较差等。本课题拟选用基因工程技术将尘螨两类最主要变应原Der f2、Der p2构建融合蛋白（DerⅡ）；同时利用纳米材料可保护抗原、增强免疫反应、缓释和副作用小的优点,制备PLGA-DerⅡ新型尘螨过敏原口服疫苗并对其表征进行分析。建立小鼠哮喘模型，对PLGA-DerⅡ口服疫苗免疫治疗及机理进行研究：对该疫苗免疫治疗疗效进行评价，观察疫苗对小肠粘膜免疫系统的作用，疫苗在过敏性哮喘动物模型体内吸收代谢；疫苗通过SHP-1和IL-10诱导免疫耐受治疗哮喘的机理。该研究可望为临床哮喘等过敏性疾病尘螨过敏原特异性免疫治疗提供新方法、新途径和理论依据。

There are 200 million allergic patients in China, more than 70% of them are sensitized to dust mites. The specific immunotherapy (SIT) is the only specific therapeutic remedy available for the treatment of allergic disorders. Published data indicate that the therapeutic efficiency of SIT is to be further improved. A number of limitations of dust mite allergen vaccines have been recognized, such as the vaccines mix with large amounts of non-mite proteins, which have the potential to trigger further allergic reactions; poor compliance of the patients during SIT is another shortcoming. In this project we will fuse Der f2 with Der p2 to a fusion protein, DerⅡ. On the other hand, nano-materials favor preserving allergens, enhancing the immune responses,sustaining –release, and having light side effects. The proposed study plans to prepare a new type of oral dust mite allergen vaccine called PLGA-DerⅡ. We will establish mouse asthma models to explore the efficacy of PLGA-Der II on suppressing the mite-specific allergic airway allergy as well as to look into its mechanism. The study aims include: (i) The preparation for PLGA-DerⅡ and observation in the metabolism of nano vaccine;(ii) the impacts of PLGA-DerⅡon related cytokins secretion; (iii) the impacts of PLGA-DerⅡon intestinal mucosal immune system;(iv) to demonstrate the role of PLGA- DerⅡin and their signal transduction pathway. The studies are expected to provide a novel approach in the study of dust mite allergen-SIT, which has the potential to be used in the treatment of allergic disorders such as asthma.