HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

病原菌表面多糖，包括囊膜 多糖类和脂多糖类可作为毒力因子 AMD保护性抗原。年龄相关免疫原性与T细胞 多糖的独立性限制了它们作为疫苗的使用。绑定到 医学上有用的蛋白质既增加了它们的免疫原性，又赋予了 T细胞对这些多糖的依赖性。婴儿被注射了 Pn6B-TT在3、4和6个月龄或7和9个月龄时仅 当地的轻微反应。三种免疫球蛋白中的抗Pn6抗体，加强剂 诱导了反应。血清免疫球蛋白与血清免疫球蛋白的相关性较好。 抗6B抗体水平与吞噬细胞对机体的杀伤 试管内。宋内氏志贺氏菌和福氏2a志贺氏菌的脂蛋白脱毒，其 O-特异性多糖与细菌类毒素结合，并被证明是 在小鼠体内具有免疫原性。1期和2期研究表明这些偶联物 是安全的，并在类似水平上诱导出长寿抗体 志贺氏菌病后的成人患者。在第三阶段试验中，S. Sonnei-REPA在志贺氏菌病暴发期间保护新兵 由这种病原体引起的。这些结合物被证明是安全的和 4-7岁儿童的免疫原性。第三阶段试验已被推迟 虽然新的和更具免疫原性的志贺氏菌结合物正在评估中 第一阶段研究。 百日咳杆菌双突变株产生无毒的CRM毒素 并且在FHA合成方面存在缺陷，正在开发中。我们的目标是 使用这种基因产生的更容易提纯的百日咳类毒素 作为肺炎球菌14型多糖的载体。 接种Pn6B-TT的婴儿用抗Pn6B应答，大多数 免疫球蛋白同型。这些抗体具有吞噬细胞的活性， 与用酶联免疫吸附试验和放射免疫法测定的水平相关。

Surface polysaccharides of pathogenic bacteria, including capsular polysaccharides and lipopolysaccharides, may serve as virulence factors amd protective antigens. The age-related immunogenicity and T-cell independence of polysaccharides limit their use as vaccines. Binding to medically-useful proteins both increases their immunogenicity and confers T-cell dependence to these polysaccharides. Infants were injected with Pn6B-TT at 3, 4 and 6 months of age or at 7 and 9 months of age with only minor local reactions. Anti-Pn6 of the three Ig classes, with booster responses, were induced. There was a good correlation between IgG anti-type 6B levels and opsonophagocytic killing of the organism in-vitro. LPS of Shigella sonnei and flexneri 2a were detoxified, their O-specific polysaccharides bound to bacterial toxoids and shown to be immunogenic in mice. Phase 1 and Phase 2 studies showed these conjugates were safe and elicited long-lived antibodies at similar levels to those of adult patients following shigellosis. In a Phase 3 trial, S. sonnei-rEPA protected army recruits during outbreaks of shigellosis caused by this pathogen. These conjugates were shown to be safe and immunogenic in 4-7 year old children. Phase 3 trials have been postponed while new and more immunogenic Shigella conjugates are being evaluated in Phase 1 studies. A double mutant of Bordetella pertussis, producing a non-toxic CRM toxin and deficient in FHA synthesis, is being developed. The objective is to use this genetically-produced and more easily purified pertussis toxoid as a carrier for pneumococcus type 14 polysaccharide. Infants immunized with Pn6B-TT responded with anti-Pn6B, mostly of the IgG isotype. These antibodies had opsonophagocytic activities, correlated to their levels as measured by ELISA and RIA.