HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

年龄相关、T无关的免疫学特性限制了 多糖的功效，包括胶囊多糖和 解毒入侵细菌的脂多糖，作为疫苗在 婴儿和免疫功能低下的成年人。共价合成方案 已设计出将多糖与蛋白质结合以增加蛋白质的 多糖的免疫原性及其对T细胞的依赖性 这些保护性抗原的免疫学特性。基于我们的 工作和随后的工作，b型流感嗜血杆菌结合物 疫苗已获得食品和药物管理局的许可，用于 对婴儿进行常规免疫。有几种结合疫苗， 其中两种目前在美国获得了用于婴儿的许可。这个 PRP-T(直接疫苗)诱导的血清抗体应答 在我们的研究之后)在北卡罗来纳州的夏洛特市进行了研究。这个 将多糖结合到蛋白质上的技术也得到了扩展 多聚α(2-gt；8)NeuNAc(B组的包膜多糖 脑膜炎球菌大肠埃希菌K1、溶血性巴氏杆菌A2型)。 一种交叉反应的大肠杆菌多糖K92，可诱导产生抗体 和相关的PolyAlpha(2-gt；9)NeuNAc(C组脑膜炎球菌) 胶囊)。这项技术也已扩展到多糖领域。 新生隐球菌、金黄色葡萄球菌和解毒者 志贺氏菌的脂多糖。第一阶段以后者为研究对象 产品已顺利完成。

The age-related, T-independent immunologic properties limit the effectiveness of polysaccharides, including capsular polysaccharides and detoxifies lipopolysaccharides of invasive bacteria, as vaccines in infants and in immunocompromised adults. Synthetic schemes to covalently bind polysaccharides to proteins have been devised to increase the immunogenicity of the polysaccharides and to confer T-cell dependent immunologic properties upon these protective antigens. Based upon our work and the work that followed, Haemophilus influenzae type b conjugate vaccines have been licensed by the Food and Drug Administration for routine immunization of infants. There are several conjugate vaccines, two are currently licensed for use in infants, in the United States. The serum antibody response induced by PRP-T (a vaccine fashioned directly after our research) was studied in Charlotte, North Carolina. The technology of binding polysaccharides to proteins has been extended also to poly alpha(2->8) NeuNAc (the capsular polysaccharide of group B meningococcus Escherichia coli K1, Pasteurella haemolytica serotype A2). A cross-reactive E. coli polysaccharide K92, elicited antibodies to this and to the related poly alpha(2->9) NeuNAc (group C meningococcus capsule). This technology has also been extended to the polysaccharides of Cryptococcus neoformans, Staphylococcus aureus and the detoxified lipopolysaccharides of Shigella. The phase 1 studies with these latter products have been completed successfully.