HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

细菌病原体的表面多糖，包括 胶囊多糖和脂多糖，起到保护作用 抗原。这些细菌多糖的免疫学性质， 即它们的年龄相关和T细胞非依赖的免疫原性，限制 它们被用作疫苗。共价依附于医学用途 形成偶联的蛋白质，既增加了它们的免疫原性，又 赋予这些多糖依赖T细胞的特性。这个 肺炎链球菌6B型衣壳多糖， 金黄色葡萄球菌5型和8型，B组链球菌3型 已与几种蛋白质结合，并进行了临床评估。金黄色葡萄球菌型 5-REPA在终末期肾病患者中的评估；5型 三个主要免疫球蛋白类的抗体显著上升到 程度低于健康志愿者，对 在6周时再次注射。这些抗体具有吞噬细胞功能。 活动。Pn6B-TT在镰状细胞病患者中进行评估， 3、4、6个月或7、9个月的健康婴儿。 三个免疫球蛋白类的类型特异性抗体，具有增强反应， 都是被诱导的。这些反应的幅度小于Hib- 好的。GBSIII-TT在育龄女性中进行评估。免疫球蛋白 与单独使用多糖的反应类似，抗三型抗体也有类似的上升。 发现了这批货的技术问题。所有的结合物都是 安全，只有轻微的局部反应。志贺氏杆菌的内毒素是 解毒后，它们的O-特异性多糖与细菌类毒素结合 它们在小鼠身上的免疫原性是令人满意的。在第一阶段 和第二阶段研究，这些O-特异性多糖的结合物 是安全的和免疫原性的：由 研究结合物与正在疗养的新兵相似。 是志贺氏菌病引起的。在初步研究中，一种S.sonnei-REPA结合物 对这种病原体引起的志贺氏菌病有保护作用。一个更广泛的 研究表明，保护率为75%。

The surface polysaccharides of bacterial pathogens, which include capsular polysaccharides and lipopolysaccharides, serve as protective antigens. The immunologic properties of these bacterial polysaccharides, namely their age-related and T-cell independent immunogenicity, limit their use as vaccines. Covalently attachment to medically-useful proteins to form conjugates, both increases their immunogenicity and confers T-cell dependent properties to these polysaccharides. The capsular polysaccharides of Streptococcus pneumococcus type 6B, Staphylococcus aureus types 5 and 8, Group B streptococcus type 3 have been bound to several proteins and evaluated clinically. S. aureus type 5-rEPA was evaluated in end stage renal disease patients; type 5 antibodies of the three major Ig classes rose significantly though to a lesser degree than in healthy volunteers, no booster response to reinjection at 6 weeks was found. These antibodies had opsonophagocytic activities. Pn6B-TT was evaluated in patients with sickle cell disease, healthy infants at 3, 4 and 6 months of age or at 7 and 9 months of age. Type specific antibodies of the three Ig classes, with booster responses, were induced. The magnitude of these responses was lesser than of Hib- TT. GBSIII-TT was evaluated in females of child bearing age. IgG antitype III rose similarly to the response to the polysaccharide alone. Technical problems with this lot were identified. All conjugates were safe, with only minor local reaction. The LPS of shigellae was detoxified, their O-specific polysaccharides bound to bacterial toxoids and their immunogennicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these conjugates of the O-specific polysaccharides were safe and immunogenic: LPS antibody levels elicited by the investigational conjugates were similar to those in recruits convalescent from shigellosis. In preliminary studies, a S. sonnei-rEPA conjugate protected against shigellosis caused by this pathogen. A more extensive study showed protection of 75%.