肺炎链球菌疫苗SPY1的一种免疫保护机制：TGF-β信号通路介导Treg细胞参与保护性免疫

项目名称： 肺炎链球菌疫苗SPY1的一种免疫保护机制：TGF-β信号通路介导Treg细胞参与保护性免疫

项目编号： No.31500749

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 徐绣宇

作者单位： 重庆医科大学

项目金额： 20万元

中文摘要： 疫苗的有效性取决于其免疫保护机制，因此，阐明疫苗的免疫保护机制是新型疫苗临床前试验的关键内容。SPY1是前期研发的肺炎链球菌减毒活菌疫苗，该疫苗毒力显著降低，遗传稳定性高，安全性好，保护效果优于现有商品化多糖疫苗。前期探索SPY1免疫保护机制时，新发现SPY1可诱导小鼠Treg免疫反应；进一步发现免疫小鼠体内TGF-β1水平升高；抑制小鼠TGF-β，Treg细胞减少，疫苗保护效果降低。推测：SPY1是否通过TGF-β信号通路诱导Treg细胞分化，并通过免疫抑制性细胞因子或共刺激分子发挥免疫调节功能，参与疫苗保护效果？因此，本研究拟通过流式细胞术、功能分类表达谱芯片、qRT-PCR、Western blot等技术，深入探讨TGF-β信号通路介导SPY1诱导特异性Treg反应，发挥免疫调节功能，参与疫苗保护的机制，为阐明SPY1疫苗的保护效应机制提供理论和实验依据。

中文关键词： 肺炎链球菌；疫苗；保护机制；TGF-β；Treg细胞

英文摘要： Vaccine effectiveness depends on the mechanism of immunizing protection elicited; therefore, claiming the protective mechanism is a key part of development of novel vaccine candidate. Pneumococcal live attenuated vaccine SPY1 was an effective vaccine candidate developed before, showing characters of reduced virulence, high genetic stability, safety, and excellent protection in mice, which was even better than that of commercially available polysaccharide vaccine. Increase in Treg cell numbers in immunized mice was innovatively found when investigating the protective mechanism of SPY1. Further, we found elevated TGF-β concentration induced by SPY1, whereas, decrease in Treg cells and impaired protection were observed as results of inhibition of TGF-β. We therefore hypothesized that SPY1 is able to induce protective Treg immune response via TGF-β signal pathway, which participate in the protection of SPY1 via some immune modulating pathways. In this research, to further investigated the detailed signal pathways by which the protective Treg immune response elicited by SPY1, as well as the molecular mechanism of SPY1-specific Treg immune response maintaining the immune homeostasis and participating in the protection induced by SPY1, techniques including qRT-PCR, flow cytometry analysis, Western blot, and DNA microarrays for gene expression profiles will be employed. Our work will further provide theoretical and experimental evidences for further research of SPY1.

英文关键词： Streptococcus pneumonia;vaccine;protective mechanism;TGF-β;Treg cells