基于伤寒沙门菌Vi抗原结构的糖疫苗研究

伤寒是很多发展中国家以及不断增多的世界流动人群面临的重要的公共卫生问题。为了解决目前应用广泛的最新代的基于Vi抗原的伤寒多糖疫苗所存在的质量控制问题，本项目拟用化学方法高效、高立体选择性地构建糖链较长（五糖以上）、结构均一的Vi抗原寡糖片段，并对其抗原活性进行评价；同时对Vi抗原寡糖结构进行模拟，设计合成系列寡糖结构模拟物，利用多价效应或者通过对寡糖连接顺序的模拟，提高合成的寡糖类化合物的抗原活性；总结构效关系，以期发现活性强的基于Vi抗原的新的伤寒合成疫苗先导结构。

Typhoid fever remains an important health threat in many parts of the developing countries and to increasing world migrant population. To solve the quality control problem of the latest and widely-used generation of vaccine against typhoid fever based on the Vi polysaccharide antigen of Salmonella typhi,in this project we will assemble the homogenous and structure-defined longer oligosaccharide fragments (more than pentasaccharide) of Vi antigen in a stereoselective and highly efficient manner by using chemical method, and evaluate the antigenic activity of these oligosaccharides. In the meantime, we will mimic the oligosaccharide structure of Vi antigen, design and synthesize a series of oligosaccharide mimetics, enhancing the antigenic activity of synthetic oligosaccharide analogues by multi-valent effects or by mimicking the sequence of oligosaccharide structure. By summarizing the structure-activity relationships, we hope to discover potent new synthetic vaccine against typhoid fever lead structures based on Vi antigen.