基于模块化组装策略快速制备细菌糖蛋白缀合物疫苗

人类社会始终面临来自传染病的严峻挑战。当有新发疫情时，实现疫苗的快速制备非常重要。寡糖蛋白质缀合物疫苗已经成为新一代糖疫苗。研究表明外核心寡糖可以刺激免疫系统产生特异性抗体，近年来成为细菌糖疫苗开发的热点。对细菌表面多糖结构分析发现，不同类型的细菌可能拥有共同糖结构单元。因此本项目设想对细菌表面多糖中外核心寡糖结构进行大数据分析，找到细菌外核心寡糖共同结构单元，利用本课题组前期建立的寡糖基转移酶介导糖蛋白质缀合物生产平台，建立含有外核心寡糖共同结构单元的糖蛋白质缀合物模块。在此基础上，利用酶法模块化组装策略，将糖蛋白质缀合物模块和不同糖链进行平行组装，快速构建结构不同的细菌外核心寡糖蛋白缀合物库，从而实现寡糖蛋白质缀合物疫苗的高通量快速制备。本项目不仅解决现有糖疫苗生产方式的局限性，实现糖疫苗的高通量快速生产，而且对于控制病原细菌突发具有重要意义。

The increasing incidence of infections caused by pathogenic microorganisms constitute a public health emergency. Glycoconjugate vaccines are proving to be the most effective strategy for controlling infections caused by pathogenic microorganisms. However, there is an urgent need to develop quick and effective methods for glycoconjugate vaccines production. Outer core oligosaccharides are potential vaccine candidates because they are densely represented on the bacterial surface and are readily accessible as targets of adaptive immunity. Consequently, glycoconjugates with well-defined outer core oligosaccharides structures , that are able to confer highly reproducible biological properties and a better safety profile, are at the forefront of vaccine development. Following on from our previous works on the subject, we specifically focus on the same structures in outer core oligosaccharides from differnt bacteria. The enzymatic modular assembly strategey will be developed to provide a quick and effective strategy for parallel synthesis of differnt outer core oligosaccaride conjugated vaccins in a few steps from readily available glycoconjugated protein as module.