HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

细菌病原体的表面多糖起着保护作用， 抗原它们的免疫学特性，即它们的年龄相关性和T- 独立免疫原性限制了它们作为疫苗的用途。共价 连接到医学上有用的蛋白质以形成缀合物， 增加其免疫原性并赋予T依赖性， 这些多糖。链球菌荚膜多糖 肺炎球菌6 B型和14型，金黄色葡萄球菌5型和8型， B链球菌3型、流感嗜血杆菌a型和埃希氏菌 coli K1与蛋白质结合，并测定其免疫学特性 对小鼠 肺炎球菌6型B和B族链球菌结合物具有 进行了临床评估。结合物诱导抗体的安全性 与E.大肠杆菌K1在幼鼠模型中进行了评价。 志贺氏菌的LPS被解毒，其O-特异性多糖结合 细菌类毒素及其在小鼠中的免疫原性， 满意在I期和II期研究中，这些O特异性 多糖是安全和免疫原性：LPS抗体水平引起的 研究偶联物与新兵相似 志贺氏菌病的康复期。在初步研究中，一个S. Sonnei-rEPA 偶联物可抵抗由该病原体引起的志贺氏菌病。 广泛的疗效试验正在进行中。

The surface polysaccharides of bacterial pathogens serve as protective antigens. Their immunologic properties, namely their age-related and T- independent immunogenicity, limit their use as vaccines. Covalent attachment to medically-useful proteins to form conjugates, both increases their immunogenicity and confers T-dependent properties to these polysaccharides. The capsular polysaccharides of Streptococcus pneumococcus types 6B and 14, Staphylococcus aureus types 5 and 8, Group B streptococcus type 3, Haemophilus influenzae type a and Escherichia coli K1 were bound to proteins and their immunologic properties assayed in mice. Pneumococcal type 6B and Group B streptococcal conjugates have been evaluated clinically. The safety of conjugate-induced antibodies reactive with E. coli K1 was evaluated in an infant rat model. LPSs of shigellae were detoxified, their O-specific polysaccharides bound to bacterial toxoids and their immunogenicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these 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. Extensive efficacy trials are underway.