Ag43嵌合疫苗通过IgE/FcɛRI通路防治变应性鼻炎的机制研究

变应性鼻炎是以IgE介导的，嗜酸性粒细胞反应为主的，由多种炎症细胞及细胞因子共同参与的I型变态反应性疾病。以IgE/FcɛRI信号通路为靶点设计药物，已成为治疗变态反应性疾病的一个新的热点。现有一种细菌表面抗原Ag43和Fcɛ嵌合蛋白能被进一步加工为蛋白疫苗，打破免疫耐受产生自身抗IgE抗体，阻断IgE/FcɛRI信号通路，干预变应性疾病桥联反应。我们拟分析此疫苗在变应性鼻炎中的潜在的治疗效用，检测鼻粘膜上皮细胞在免疫、炎症反应和组织重塑相关指标，客观评价Ag43嵌合细菌表面抗原蛋白疫苗对变应性鼻炎的疗效和后续应用价值。检测IgE/FcɛRI通路中IgE、FcɛRI受体的表达，分析鼻粘膜组织上肥大细胞的脱颗粒的改变，探索下游肥大细胞分泌降低后相关细胞炎性介质因子平衡的改变与IgE生成降低的关系，研究此抗体在桥联环节中的缺失及其突破免疫耐受的具体机制，并以此建立一套更有效的防治策略。

Allergic rhinitis is an allergic diseases in which IgE mediated, eosinophils as a main reaction and a lot of inflammatory cells and cytokines participate. Targeting IgE/FcɛRI as a signaling pathway drug design has become a new targets and hot spot in the drug research of allergic disease treatment.There is a Ag43/Fcs chimeric bacterium surface antigen protein which can break of the immune tolerance against IgE antibody, blocked IgE/FcɛRI signal pathway, intervene allergic disease bridging reaction through the further preparation as protein vaccine. We intend to analyze the potential therapeutic utility of this vaccine in allergic rhinitis, examine the correlation of nasal mucosal epithelial cells in the immune response and inflammatory response as well as tissue remodeling，then evaluate the efficacy.The effect of the vaccinationis is searched in allergic rhinitis, through testing IgE and FcɛRI expression of receptors prove that it blocked IgE/FcɛRI signal pathway, analyzing the change of mastocyte degranulation of nasal mucous samples, testing balance changes of related cell inflammatory mediator factor by means of detecting downstream that mastocyte`s secretion is lowered, proving that effect of reducing of IgE production, further studying on this vaccine subsequent mechanism of action and design more perfect vaccine or combined treatment to allergic rhinitis and a set of more effective treatment strategy will be established.