靶向抗原特异性T细胞融合蛋白疫苗的构建及其抑制过敏性哮喘的机理研究

Along with the increasing seriousness of environmental pollution, the global total prevalence of allergic asthma disease is rising, which serious harm human health. Allergic asthma is a common respiratory inflammatory disease; the key factor of its pathogenesis is the imbalances of Th1 / Th2 response in the airway mucosa, in which the Th1 response cannot effectively counteract the activation of Th2 inflammatory. Currently, fusion protein vaccines targeting at allergic asthma are still at the exploratory stage. Based on previous research work and the preliminary study, this research intends to construct a fusion protein vaccine, which targets to induce allergen specific T cells to express and produce the Th1 cytokine to counteract the Th2 polarization in the airway mucosa of asthma mice and study its effect on inhibiting the allergic inflammation in the airway mucosa of asthma mice. Furthermore, we will also elucidate the mechanism by which the fusion protein vaccines inhibit allergic asthma. The expected results will provide a novel and effective therapeutic remedy for the treatment of allergic asthma.

随着环境污染的日益严重，全球过敏性哮喘疾病患病率不断攀升，严重危害人类的健康。过敏性哮喘是一种常见的呼吸道炎症性疾病，其发病机制的关键因素是机体内Th1/Th2细胞的失衡。目前，国内外在融合蛋白疫苗靶向性治疗过敏性哮喘疾病研究方面仍处于探索阶段。本研究拟在前期研究工作基础上创新性地构建一种靶向性过敏原特异性T细胞并诱导细胞产生适量的Th1型细胞因子从而维持免疫系统稳态的融合蛋白疫苗；同时明确该融合蛋白疫苗靶向性治疗过敏性哮喘疾病的效果；进一步阐明融合蛋白疫苗治疗过敏性哮喘的作用机制，有望为过敏性哮喘疾病的治疗提供一种新型高效的生物治疗方法。

过敏性哮喘是一种常见的呼吸道炎症性疾病，目前全球过敏性哮喘患者超过3.39亿，而其发病机制的关键因素是机体内Th1/Th2细胞的失衡。目前对过敏性哮喘的治疗措施有限且疗效不满意。因此，恢复机体免疫系统Th1/Th2的平衡对发掘新的抗过敏疗法有重要意义。我们在本研究中构建了一种可靶向抗原特异性T细胞并直接进入细胞中的tTIM融合蛋白疫苗，并观察到tTIM疫苗能够调节抗原特异性T细胞的分化，抑制Th2细胞的极化从而恢复机体免疫系统的稳态。我们在本研究中完成了以下内容：（1）构建了可靶向抗原特异性T细胞的tTIM疫苗；（2）确定了tTIM疫苗的安全性及最佳治疗剂量；（3）观察了tTIM疫苗对肺组织粘膜Ag特异性T细胞的调节作用；（4）观察了tTIM疫苗抑制抗原特异性Th2分化的作用机制。这些研究结果进一步加深了对过敏性哮喘患者免疫系统失衡机制的认识，同时也为促使失衡的免疫系统恢复稳态提供了一种新的疗法并为临床上治疗因免疫系统稳态失衡而引起的过敏性疾病提供了一种新的思路。