HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

包括囊膜在内的细菌病原体的表面多糖 多糖和脂多糖作为保护性抗原。 这些细菌多糖的免疫学性质即 它们的年龄相关和T细胞非依赖性免疫原性限制了它们的使用 作为疫苗。共价连接到医学上有用的蛋白质上，形成 共轭关系。两者都增强了它们的免疫原性，并赋予T细胞 依赖于这些多糖的性质。囊状物 6B型肺炎链球菌的多糖已结合到 破伤风类毒素和临床评估。金黄色葡萄球菌5-repa是 在终末期肾病患者中进行评估；5型抗体 三个主要的免疫球蛋白课程显著增加，尽管程度较小 与健康的志愿者相比。正如预期的那样，没有助推器 对重新注射的反应。这些疫苗诱导的抗体具有 吞噬细胞的吞噬功能。对Pn6B-TT进行评估的患者 镰状细胞病，3、4和6个月大或 7个月和9个月大。三种Ig类的类型特异性抗体， 与增强反应，是诱导的。这些反应的大小 低于Hib-TT。所有的结合物都是安全的，只有少量的 当地的反应。志贺氏菌的内毒素被解毒，其0特异性 细菌类毒素结合的多糖及其免疫原性 老鼠被发现是令人满意的。在第一阶段和第二阶段研究中，这些 0特异性多糖的结合物是安全的和免疫原性的： 由研究结合物引起的脂蛋白抗体水平为 与志贺氏菌病疫苗康复期的新兵相似- 诱导的免疫球蛋白在较高水平持续两年。在预赛中 尽管有统计学意义的研究，一种宋内氏链球菌-REPA结合物 对这种病原体引起的志贺氏菌病有保护作用。第二阶段研究 儿童体内的宋内氏链球菌和福氏志贺氏菌的结合体均为 高度安全且具有免疫原性。第三阶段的试验正在计划中。

The surface polysaccharides of bacterial pathogens including 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 have been bound to tetanus toxoid 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 compared to healthy volunteers. As expected, there was no booster response to reinjection. These vaccine-induced 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. All conjugates were safe, with only minor local reaction. The LPS of shigellae was detoxified, their 0-specific polysaccharides bound to bacterial toxoids and their immunogenicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these conjugates of the 0-specific polysaccharides were safe and immunogenic: LPS antibody levels elicited by the investigational conjugates were similar to those in recruits convalescent from shigellosis vaccine- induced IgG persisted at high levels for two years. In preliminary though statistically significant studies, a S. sonnei-rEPA conjugate protected against shigellosis caused by this pathogen. A phase 2 study of S. sonnei and S. flexneri in children showed both conjugates to be highly safe and immunogenic. Phase 3 trials are being planned.