Toll样受体（Toll-like receptors，TLRs）激动剂是目前新型佐剂研究的热点，鞭毛蛋白（FliC）是目前已知的唯一一种天然TLR5激动剂，然而FliC及其活性衍生物化学本质都是蛋白质或多肽，不可避免地会诱导机体对其产生获得性免疫应答，导致耐受。本项目综合分析现有TLR5激动剂的缺陷及原因，借鉴现代分子生物学、物理化学及免疫学理论技术，结合前期佐剂研究基础，拟优化构建自活化TLR5 mRNA佐剂系统，通过DOTAP阳离子脂质体递送TLR5及其激动剂CBLB502 mRNA，使二者在胞内翻译并互作形成信号复合物，引起固有免疫应答，发挥佐剂效应，不依赖细胞表面的TLR5，且避免了现有TLR5激动剂的不足。进一步通过细胞水平、动物整体水平对其免疫应答谱学特征及机制进行系统研究。本项目若成功，可为疫苗佐剂的设计提供新的思路，为基于自活化mRNA原理设计佐剂提供理论及实践的基础。

Toll-like receptors (TLRs) agonists are currently the focus of research on new adjuvants. Flagellin (FliC) is the only known natural TLR5 agonist, but FliC and its active derivatives are proteins or peptides, which will inevitably induce the body to produce an adaptive immune response to it, leading to tolerance. This project comprehensive analysis of the existing defects and the reasons of TLR5 agonist, use the theory of modern molecular biology, physical chemistry and immunology technology, combine with early adjuvant research foundation, and then propose to optimize building the auto active TLR5 mRNA adjuvant system, TLR5 and its agonist’s mRNA can be delivered through the DOTAP cationic liposomes and then both in intracellular translation and interactions to form complex signal, initiates the innate immune response, avoids the deficiencies of existing TLR5 agonists. The spectrum characteristics and mechanism of the innate and adaptive immune response were further systematically studied at the cell and the animal level. If successful, this project will provide new strategy for the design of vaccine adjuvants, and provide theoretical and practical basis for the design of adjuvants based on the principle of auto activate mRNA.