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铜绿假单胞菌相关聚糖的合成及免疫学研究进展

Research progress on the synthesis and immunological studies of Pseudomonas aeruginosa-related to glycans

  • 摘要: 铜绿假单胞菌是一种多重耐药的机会性致病菌,可引发严重的院内感染。其表面的脂多糖及胞外多糖是糖缀合物疫苗开发的关键靶点。化学合成能提供结构明确、均一、无污染的寡糖抗原,为精准表位鉴定和合理疫苗设计奠定基础。本文系统综述了该菌相关聚糖的化学合成及免疫学研究进展。合成策略涵盖线性组装、汇聚式糖基化、一锅多组分合成及糖基化后氧化。针对1, 2-顺式糖苷键的立体选择性构建、稀有脱氧氨基糖的引入、正交保护及后期非糖修饰等挑战,总结了有效解决方案。文中详述了O1、O3、O4、O5、O7、O10、O11、O17、O19、ATCC 27577、NCTC 8505等血清型O-抗原、核心寡糖及胞外多糖(藻酸盐、Psl、Pel)片段的成功合成案例。免疫学研究方面,介绍了基于单克隆抗体与患者血清的表位识别,以及通过糖芯片筛选关键抗原决定簇。多个CRM₁₉₇缀合物可诱导强效的T细胞依赖性IgG应答,并在动物模型中提供广谱保护。最后,分析了当前面临的挑战(合成效率低、立体控制不足、免疫评价不系统)以及未来的发展方向。本文旨在为铜绿假单胞菌合成糖缀合物疫苗的研发提供参考。

     

    Abstract: Pseudomonas aeruginosa is a multidrugresistant opportunistic pathogen causing severe nosocomial infections. Its surface lipopolysaccharide and exopolysaccharides are key targets for glycoconjugate vaccine development. Chemical synthesis provides structurally defined, homogeneous and contaminant-free oligosaccharide antigens, enabling precise epitope identification and rational vaccine design. This review systematically summarizes recent advances in the chemical synthesis and immunological evaluation of P. aeruginosaassociated glycans. Synthetic strategies include linear assembly, convergent glycosylation, onepot multicomponent synthesis and postglycosylation oxidation. Solutions to challenges such as stereoselective construction of 1, 2-cis-glycosidic linkages, introduction of rare deoxy amino sugars, orthogonal protection and latestage nonsaccharide modifications are highlighted. Successful syntheses of Oantigen repeating units from serotypes O1, O3, O4, O5, O7, O10, O11, O17, O19, ATCC 27577, NCTC 8505, core oligosaccharides, and exopolysaccharide fragments (alginate, Psl, Pel) are described. On the immunological front, epitope recognition using monoclonal antibodies and patient sera, as well as glycan microarray identification of key antigenic determinants, are discussed. Several CRM₁₉₇ conjugates induced strong Tcelldependent IgG responses and provided broad protection in animal models. Current challenges (low synthetic efficiency, insufficient stereocontrol, unsystematic immunological evaluation) and future directions are analyzed. This review aims to guide the development of synthetic glycoconjugate vaccines against P. aeruginosa.

     

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