HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

细菌病原体的表面多糖包括荚膜多糖 多糖和脂多糖用作保护性抗原。 这些细菌多糖的免疫学特性，即 它们的年龄相关的和不依赖于T细胞的免疫原性限制了它们的应用 as vaccines疫苗.粘附在医学上有用的蛋白质上， 共轭都增加了它们的免疫原性，并赋予T细胞 依赖于这些多糖的性质。囊 肺炎链球菌6 B型的多糖已经结合到 破伤风类毒素和临床评价。 S.金黄色葡萄球菌5型-rEPA是 在终末期肾病患者中进行评估; 三个主要的IG类显著上升，尽管程度较小 与健康志愿者相比。 不出所料，没有助推器 回复回复回复 这些疫苗诱导的抗体 调理吞噬活性。Pn 6 B-TT在患有以下疾病的患者中进行了评价： 镰状细胞病，3、4和6个月大的健康婴儿或 7和9个月大。 三种IG类的型特异性抗体， 与加强反应，被诱导。 这些反应的强度 低于Hib-TT。 所有结合物都是安全的， 当地反应。 志贺氏菌的LPS被解毒，它们的0-特异性 与细菌类毒素结合的多糖及其免疫原性 小鼠被认为是令人满意的。 在1期和2期研究中，这些 0-特异性多糖的缀合物是安全的和免疫原性的： 由研究性缀合物引发的LPS抗体水平为 与接种志贺氏菌病疫苗后恢复期的新兵相似， 诱导的IgG持续高水平两年。 初步 尽管有统计学意义的研究，一个S。Sonnei-rEPA结合物 防止由这种病原体引起的志贺氏菌病。 一项2期研究 色葡萄sonnei和S.在儿童的flexneri表明，这两种结合物是 高度安全和免疫原性。 3期试验正在计划中。

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.