HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

嗜血杆菌的年龄相关和T非依赖性免疫学特性 乙型流感衣壳多糖和其他乙型流感病毒多糖 入侵细菌限制了它们作为疫苗对婴儿和婴儿的保护作用 儿童，疾病发病率最高的年龄段 这些病原体。一种通用的有机合成方案，可以结合H. B型流感病毒和其他衣壳多糖对载体蛋白的影响 是为了增加免疫原性和赋予 T细胞对这些保护性抗原的依赖性(增强效应)。基于 我们和别人的工作，我们研制的一种结合的Hib疫苗 最初的方法被美国食品和药物管理局批准在儿童中普遍使用 超过18个月大的。现在，许可证已扩展到其他 共轭药物和这些新产品的上市后监测成功 已将年龄限制降至15个月。我们已经证明了我们的H. 乙型流感病毒-破伤风类毒素结合物既安全又具有免疫原性 3、5、7和18个月大的婴儿(推荐时间表 婴儿疫苗)。大约75%的婴儿产生了保护水平的 一次注射抗体，第三次注射后全部获得保护 注射。对载体诱导产生保护性水平的抗体 蛋白质也是。这项技术已经扩展到B群链球菌 III型、新生隐球菌属和B群囊型脑膜炎球菌 迄今为止被认为不具有免疫原性的多糖类。高 这种结合物在体内诱导了对这种聚合物的抗体水平 老鼠。两批12F-DT肺炎球菌结合物成人评价 志愿者被发现是安全的，并能诱导更高水平的12F 抗体水平高于未结合的CP疫苗。以较高的价格抽签 MW CP诱导产生较高的抗体水平。葡萄球菌5型结合物 或8和铜绿假单胞菌外毒素A显示免疫原性增强 和小鼠的T细胞依赖特性。

The age- related and T-independent immunologic properties of Haemophilus influenzae type b capsular polysaccharide and other polysaccharides of invasive bacteria limit their protective actions as vaccines in infants and children, the age group with the highest attack rate of disease due to these pathogens. A general organic synthetic scheme, that could bind H. influenzae type b and other capsular polysaccharides to carrier proteins was devised in order to both increase the immunogenicity of and confer T-cell dependence (booster effect) to these protective antigens. Based upon our, and the work of others, a conjugated Hib vaccine prepared by our original method was licensed by the FDA for universal use in children greater than 18 months of age. Now, a license has been extended to other conjugates and the postmarketing surveillance success of these new products has lowered the age limits to 15 months of age. We have shown that our H. influenzae type b-tetanus toxoid conjugate is both safe and immunogenic in infants at ages 3, 5, 7 and 18 months of age (recommended schedule for infant vaccines). About 75% of the infants developed protective levels of antibody with one injection and all were protected after the third injection. Protective levels of antibodies were induced to the carrier protein as well. This technology has been extended to Streptococcus group B type III, Cryptococcus neoformans and to group B meningococcus capsular polysaccharide which, heretofore, has been considered nonimmunogenic. High levels of antibodies to this polymer were induced by this conjugate in mice. Two lots of pneumococcus type 12F-DT conjugate evaluated in adult volunteers were found to be safe and induce higher levels of type 12F antibodies than the unconjugated CP vaccine. The lot made with the higher MW CP induced higher antibody levels. Conjugates of staphylococcal types 5 or 8 and Pseudomonas aeruginosa exotoxin A showed increased immunogenicity and T-cell dependent properties in mice.