SYNTHETIC VACCINE AGAINST SHIGELLOSIS II--SHIGELLA SONNEI

抗志贺氏菌 II 型合成疫苗--宋内志贺氏菌

• 批准号: 6162489
• 负责人: V POZSGAY
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162489
• 关键词: Shigella; Shigella dysenteriae; Shigella vaccines; bacterial polysaccharides; carbohydrate structure; immunoconjugates; nuclear magnetic resonance spectroscopy; oligosaccharides; synthetic vaccines; vaccine development

Shigella sonnei is a major causative organism of shigellosis worldwide, that appears the most prevalent of Shigellae in developed countries. We are developing synthetic oligosaccharide-based immunogens as possible vaccine candidates against this organism using an approach similar to the synthetic vaccine project targeting a conjugate vaccine against S. dysenteriae type 1. The O-SP of S. sonnei consists of a disaccharide repeating unit containing the unique sugars 2-acetamido-2-deoxy-l-altruronic acid and 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose in a- and b-linked form, respectively. Using nuclear magnetic resonance spectroscopy we found that this polysaccharide has a zwitterionic structure with opposite charges at each consecutive residue. Starting from l-glucose and d-glucosamine, we synthesized the monosaccharide components of this polysaccharide the first time as their methyl glycosides in their natural anomeric configuration. NMR studies indicated that the trideoxy-galactose component exists in the 4C1 conformation whereas the conformations of the altruronic acid derivatives depend on their substitution pattern. The free uronic acid exists as an equilibrium mixture of the 4C1 and 1C4 chair conformers. We published complete assignments for the 1H and 13C NMR spectra of the O-SP and presented evidence that both pyranose residues in the polysaccharide exist in the 4C1 conformation. We have designed synthetic schemes for the assembly of the disaccharide repeating unit and for larger oligosaccharides of the O-SP of S. sonnei.

宋内氏志贺氏菌是世界范围内引起志贺氏菌病的主要病原菌， 这似乎是发达国家最普遍的志贺氏菌。我们 正在尽可能地开发基于低聚糖的人工免疫原 使用一种类似于 合成疫苗项目，目标是针对S。 宋内氏志贺氏菌的O-SP由二糖组成 含有独特糖类的重复单元 2-乙酰氨基-2-脱氧-L-尿囊酸和 A-和b-连接形式的2-acetamido-4-amino-2，4，6-trideoxy-d-galactose， 分别进行了分析。利用核磁共振波谱，我们发现 这种多糖具有两性离子结构，与之相反 在每个连续的残留物上充电。从L开始-葡萄糖和 D-氨基葡萄糖，我们合成了它的单糖成分 首次将多糖作为其天然的甲基苷 异常配置。核磁共振研究表明，三脱氧半乳糖 组分存在于4c1构象中，而 尿醛酸衍生物取决于它们的取代模式。这个 游离的糖醛酸以4C1和1C4的平衡混合物的形式存在 座椅变形器。我们发表了1H和13C的完整作业 O-SP的核磁共振谱和吡喃糖的证据 多糖中的残基以4c1构象存在。我们有 设计了二糖重复组装的合成方案 单位和宋内氏链霉菌O-SP中较大的寡糖。