基于功能化M13噬菌体构建仿生型时序响应的流感疫苗及其抗病毒作用研究

流感流行严重威胁着人类健康及经济发展，发展高效的流感疫苗迫在眉睫。CD8+T淋巴细胞对于清除胞内寄生的流感病毒至关重要，调控树突状细胞（DC）抗原递呈途径有利于充分调动CD8+T淋巴细胞。本课题模拟流感病毒感染机制及DC内环境刺激，提出了仿生时序响应策略用于调控DC内递呈途径，并构建新型流感疫苗。以兼具免疫佐剂与载体功能的M13噬菌体共载流感病毒血凝素（HA）与核蛋白（NP）基因，以介孔硅为基质材料，通过可逆的硼酸酯键及静电作用组装噬菌体-介孔硅纳米疫苗。其中，HA兼具受体结合活性、溶酶体pH响应性及抗原活性，利用其溶酶体破坏功能及纳米体系的pH、还原敏感时序响应，促进DC内交叉递呈；通过研究疫苗的制备工艺、胞内过程、免疫效应及抗病毒作用，探讨仿生时序响应策略对CD8+T淋巴细胞免疫应答的诱导效应。本课题的实施将为发展新型噬菌体载体疫苗奠定基础，具有重要的科学意义与研究价值。

There is an urgent demand to develop highly effective influenza vaccines because pandemic influenza threatens human's health and economic development. CD8+ T cells are critical for clearing intracellular influenza virus, which can be inducted by modulating antigen presentation pathway of dendritic cells (DC). In this study, we propose biomimetic sequence-responsive influenza vaccines, which enhance specific CD8+ T cells response. We construct the vaccine particle by employing a M13 bacteriophage harboring hemagglutinin (HA) and nucleoprotein (NP) gene, which are coated on the surface of mesoporous silica nanoparticles (MSN) through reversible borate ester bond and electrostatic interaction. We will systematically study the preparation method, antigen presentation pathway of DC, immune protection effects, the induction of CD8+ T cells response through modulating presentation pathway by HA, and as well the targeting delivery by sequence-response in DC. This innovative strategy has the potential to provide a new phage-based vaccine platform.