尘螨Der Ⅱ融合蛋白靶向双功能纳米疫苗免疫治疗的实验研究

在我国哮喘患者约3000万，其中70-80%对尘螨过敏；尘螨疫苗特异性免疫治疗（SIT）是WHO推荐的唯一对因治疗方法；但现有尘螨疫苗仍有许多不足之处。本课题在前期工作基础上①选用基因工程技术将屋尘螨和粉尘螨最主要Ⅱ类过敏原构建融合蛋白Der Ⅱ，制备新型PLGA-b-PEG纳米共聚物，以此为载体包裹具有免疫调节作用的ISS-ODN和Der Ⅱ融合蛋白；根据DC表面受体能特异性识别及结合末端含岩藻糖基载体的特性，以岩藻糖为靶向分子与上述尘螨融合蛋白纳米疫苗偶联，制成双功能尘螨Der Ⅱ靶向纳米疫苗，对该疫苗的性状和表征进行分析。②建立尘螨哮喘动物模型，观察：A、该疫苗在体内吸收和代谢；B、尘螨Der Ⅱ靶向纳米疫苗免疫治疗疗效的观察，重点是对DC和Treg的作用。③体外细胞实验进一步验证该疫苗对DC和Treg的作用及探讨其信号传导通路。该研究可望为尘螨过敏性疾病SIT提供新方法和新理论。

It is estimated more than 30 million asthmatic pateints in China; about 70%-80% patients are senaitized to dust mite among them.The antigen specific immunotherapy is the only specific therapeutic remedy for the treatment of asthma currently, which is recommended by WHO.The designed project plan to (1) generate a fusion protein of mite allergen, Der II. We will construct a nanometric vaccine containing the mite allergen, Der II, ISS-ODN and a fucose base; the latter can be specifically recognized by dendritic cells; thus, the vaccine can be specifically captured by dendric cells and to regulate the dendritic cells’ functions. We will also briefly characterize this new nanometric vaccine. (2) An asthmatic animal model will be developed to observe the (a) absorption and metabolism of the nanometric vaccine in the body; (b) therapeutic effect of the nanometric vaccine on the asthmatic animals; the effect of the nanometric vaccine on generation of toleragenic dendritic cells and regulatory T cells. (3)The signal transduction pathway will be also investigated. The expected results will provide new therapeutic method for the treatment of asthma and furhter understand the pathogenesis of the disorders caused by dust mite allergens.