肺炎链球菌融合蛋白DnaJ-∆A146Ply是申请人前期基于新型粘膜免疫佐剂——ΔA146Ply研发的一种新型的融合蛋白疫苗，粘膜免疫小鼠后，能特异性减少细菌在小鼠鼻咽部的定植，并能激发疫苗特异性的Th17型免疫应答，但是相关分子机制尚不清楚。因此，本研究拟首先利用体外细胞模型和小鼠模型，通过流式细胞术、荧光定量PCR、抗体阻断、ELISA等方法，探讨DnaJ-ΔA146Ply引起DC细胞活化及诱发获得性Th17免疫通路的受体及细胞因子机制，然后利用IL-17A缺陷鼠模型深入研究DnaJ-ΔA146Ply融合蛋白疫苗诱导的特异性IL-17A对中性粒细胞和分泌性IgA的作用。本研究可为该疫苗的进一步研发提供理论依据，并为构建其他基于ΔA146Ply构建s.pn蛋白疫苗乃至其它菌种蛋白疫苗提供新的研究思路。

Streptococcus pneumoniae fusion protein DnaJ-ΔA146Ply is a new type of fusion protein vaccine developed by the applicant based on the new type of mucosal immune adjuvant--ΔA146Ply. After immunized mice, it can specifically reduce the number of bacteria in the nasopharynx of mice colonization, and can stimulate the vaccine specific Th17 immune response, but the relevant molecular mechanism is not clear. Therefore, this study is to use the in vitro cell model and mouse model, through flow cytometry, fluorescence quantitative PCR, antibody blocking, ELISA and other methods to explore the receptors and cytokines participate in the DnaJ-ΔA146Ply induced DC cell activation and acquisition Th17 immune response. And then the effect of IL-17A induced by DnaJ-ΔA146Ply fusion protein vaccine on neutrophils and secretory IgA will be studied using IL-17A KO mice. This study can provide a theoretical basis for the further development of the vaccine and provide new research ideas for constructing other protein vaccine based on ΔA146Ply to prevent s.pn and other bacteria.