HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

本项目关注的是年龄相关和与T无关的性质 多糖类，包括胶囊多糖和解毒类 脂多糖，限制其作为疫苗的用途(有效性) 适用于婴幼儿和免疫缺陷患者。 致病多糖共价结合的合成方案 细菌到医学上有用的蛋白质的设计是为了改善 这些保护性抗原的免疫学特性。多糖类- 已经合成了针对6B型肺炎球菌的蛋白质结合物， 14型肺炎球菌，囊膜多聚α-(2-)-D-NeupNAc B群脑膜炎球菌和大肠杆菌K1的多糖， 志贺氏菌、甲型流感嗜血杆菌、新生隐球菌和 金黄色葡萄球菌。对这些结合疫苗的评估载于 不同阶段，从实验室标准化到第三阶段试验 功效。此外，聚核糖醇磷酸盐，一种交叉的多糖- 分离到与b型流感嗜血杆菌有反应性，其 表征和用作当前许可的共轭化合物的添加剂 针对这种病原体的疫苗正在评估中。这项工作仍在进行中 进步。

This project focusses on the age-related and T-independent properties of polysaccharides, including capsular polysaccharides and detoxified lipopolysaccharides, limit their usefulness (effectiveness) as vaccines for infants, young children and patients with immunologic deficiencies. Synthetic schemes for covalently binding the polysaccharides of pathogenic bacteria to medically useful proteins have been designed to improve the immunologic properties of these protective antigens. Polysaccharide- protein conjugates have been synthesized for pneumococcus type 6B, pneumococcus type 14, the poly alpha-(2->8)-D-NeupNAc the capsular polysaccharide of both Group B meningococcus and Escherichia coli K1, Shigella sp., Haemophilus influenzae type a, Cryptococcus neoformans and Staphylococcus aureus. Evaluation of these conjugate vaccines is at various stages, from laboratory standardization to Phase 3 trials of efficacy. In addition, polyribitol phosphate, a polysaccharide cross- reactive with H. influenzae type b has been isolated and its characterization and use as an addition to the current licensed conjugate vaccines for this pathogen is being evaluated. This work is still in progress.