空肠弯曲杆菌HS:2血清型荚膜多糖的化学酶法合成与免疫活性研究

空肠弯曲杆菌(C.jejuni)是引起腹泻疾病最为常见的病原体之一，并可导致诸多严重并发症。临床常规的抗生素治疗已产生了多重耐药菌株，因而开发基于C.jejuni荚膜多糖的新型糖蛋白结合疫苗有望为C.jejuni的防治提供新的解决方案。然而，由于C.jejuni荚膜多糖结构复杂，合成极具挑战性，使得相关糖蛋白缀合物的研究工作进展缓慢。由此，本项目计划针对引起C.jejuni感染最常见血清型之一的HS:2的荚膜多糖开展合成与应用研究，主要内容包括：(1)发展新的化学酶法合成策略，实现HS:2四糖重复单元中结构独特的D-甘油-L-葡萄糖型庚糖的高效合成；(2)实现HS:2四糖重复单元及二聚体和三聚体的首次人工合成；(3)将所合成糖链分别与CRM197蛋白共价结合得到系列糖缀合物疫苗，并进行免疫活性评价。该研究有望解决HS:2荚膜多糖的获得性挑战，为C.jejuni感染的防治提供新的解决途径。

C. jejuni is one of the most common pathogens causing diarrhea around the world, which can lead to numerous complications and seriously threatens mankind’s health. In clinical practice, conventional antibiotic treatment for resisting C. jejuni infection has produced multidrug-resistant strains. Therefore, the development of novel glycoprotein conjugate vaccine based on C. Jejuni capsular polysaccharides is promising for the prevention of C. jejuni infections. However, owning to the structural complexity of C. jejuni capsular polysaccharides, the synthesis of these polysaccharides is very challenging which greatly hampered the research progress of vaccine-based immunotherapy. Thus, this project plans to study the synthesis and application of HS:2 capsular polysaccharides, which is one of the most common serotypes of C. jejuni infection. The main contents for this project include: (1) development a new chemical enzymatic synthesis approach to efficiently synthesize the unique D-glycerin-L-glucose heptose unit of HS:2 tetrasaccharide repeat unit; (2) completion the first total synthesis of HS:2 tetrasaccharide repeat unit, dimer and trimer; (3) coupling of synthetic glycans with CRM197 carrier protein to obtain a series of glycoprotein conjugates, and evaluate the immune activity of glycoprotein conjugates. This study will help to solve the problem of the availability of SH:2 capsular polysaccharides, and provide a new solution for the prevention and treatment of C. jejuni infection.