生物法多糖结合疫苗的精确提呈设计和尺寸优化

多糖结合疫苗具有良好的免疫效果，产生了巨大的社会和经济效益。本研究前期工作建立了一种新的多糖结合疫苗生产策略：通过合成生物学方法，利用脑膜炎奈瑟氏菌蛋白质O-糖基化系统在细菌体内进行多糖与蛋白的偶联；成功解析并优化此系统的糖基化识别基序。本研究将在前期糖基化平台的基础上，利用最优基序进一步改进疫苗的设计：增加可与MHC-II结合的抗原提呈肽（5-6种候选），优化多糖提呈效率；增加多聚化结构域（2-3种候选），增加疫苗颗粒大小。本研究将对上述改造方式中产生的多糖-蛋白产物进行免疫评价，筛选每种改造方式中的最优方案，并进一步进行组合评估，完成新型多糖结合疫苗的精准设计与改造优化。本研究提出的新型疫苗设计思路，可设计出更为高效的多糖结合疫苗，并可用于研发各种病原菌多糖结合疫苗，具有通用性和前沿性，对细菌性传染病的感染预防具有重要意义。

Polysaccharide conjugate vaccines have good Immune effects, resulting in huge social and economic benefits. Our preliminary works have established a new synthetic biology method for conjugate vaccine production: covalently attaching the bacterial O-antigen polysaccharide to a carrier protein in vivo with the help of Neisseria Meningitidis protein O-linked glycosylation system and having found out and optimized the recognition motif of this O-linked glycosylation system using molecular biology method. So on the basis of previous work, we could design new vaccines using the optimal motif for further improvement. It can be fused with T-cell epitopes (5-6 candidates) to optimize polysaccharide presenting efficiency. On the other hand, a multimerization domain (2-3 candidates) can be added into the sequence of carrier protein to increase particle size of the new vaccine. The immunological evaluation of each kind of polysaccharide-protein products will be performed in this study. And the best one of candidates from different groups will be further combined to complete the precise design of novel polysaccharide conjugate vaccine. This new vaccine design ideas presented here can be used to develop a variety of bacterial polysaccharide conjugate vaccines with better effect. This strategy is common and cutting-edge, and important for the prevention of infectious diseases.