HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

多糖蛋白结合疫苗的人体免疫反应

• 批准号: 3857156
• 负责人: R SCHNEERSON
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3857156
• 关键词: Cryptococcus neoformans; Escherichia coli; Haemophilus influenzae; Haemophilus influenzae vaccines; Neisseria meningitidis; Neisseria meningitidis vaccine; Pasteurella; Pseudomonas aeruginosa; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pneumoniae vaccine; Streptococcus vaccine; antibacterial antibody; bacterial antigens; bacterial capsules; bacterial polysaccharides; bactericidal immunity; cellular immunity; child (0-11); drug adverse effect; human subject; immunization; immunoconjugates; immunoglobulins; immunological substance; infant human (0-1 year); laboratory mouse

The age-related, T-independent and poor immunologic properties of polysaccharides limit the effectiveness of capsular polysaccharides (CP) and other surface polysaccharides of invasive bacteria as vaccines, in infants and adult individuals with immunocompromised states. Organic synthetic schemes, that bind capsular and other polysaccharides to carrier proteins have been devised to increase the immunogenicity of and confer T-cell dependent immunologic properties (booster effect) to these protective antigens. Based upon our and others work, a conjugated Haemophilus influenzae type b (Hib) vaccine, has been licensed by the Food and Drug Administration for routine infant immunization along with DTP. Serum antibodies to Hib conjugates and to the other components of the routine immunization (DTP), have been assayed among infant recipients of our vaccine in the United States and in Sweden. This technology has been extended successfully to poly alpha(2->8) NeuNAc CPs (group B meningococcus, E. coli KI, Pasteurella haemolytica serotype A2) by multipoint attachment of this polymer to proteins at neutral pH. It was found that a cross-reactive E. coli polysaccharide, K92, elicited antibodies to this and to the related group C meningococcus CP. This technique was also extended to the CP of Cryptococcus neoformans serogroup A. More detailed studies of the conjugation procedure have revealed more effective "spacer" arms for both this conjugate and for Staphylococcus aureus CP bound to the recombinant Pseudomonas exoprotein A. Conjugates of these vaccines showed increased immunogenicity and T-cell dependent properties in mice. Further, the S. aureus type 5 polysaccharide, bound to the recombinant protein, has been successfully evaluated in phase 1 human studies.

年龄相关、T 独立且免疫学特性较差 多糖限制荚膜多糖 (CP) 的功效 和其他入侵细菌的表面多糖作为疫苗， 患有免疫功能低下状态的婴儿和成人。 有机的 将荚膜和其他多糖与载体结合的合成方案 蛋白质被设计来增加免疫原性并赋予 T 细胞依赖性免疫特性（增强效应） 保护性抗原。 基于我们和其他人的工作，共轭 b 型流感嗜血杆菌 (Hib) 疫苗已获得食品和药物管理局许可 以及常规婴儿免疫接种和 DTP 的药物管理。 Hib 结合物和其他成分的血清抗体 常规免疫接种（DTP）已在婴儿接受者中进行了检测 我们在美国和瑞典的疫苗。 这项技术已被 成功扩展到聚 α(2->8) NeuNAc CP（B 组 脑膜炎球菌、大肠杆菌 KI、溶血性巴氏杆菌 A2 型） 该聚合物在中性 pH 值下与蛋白质多点附着。 原来是 发现交叉反应性大肠杆菌多糖 K92 引发 针对该抗体和相关 C 组脑膜炎球菌 CP 的抗体。 这 该技术还扩展到新型隐球菌血清群的 CP A. 对接合过程的更详细研究揭示了更多 对于该结合物和葡萄球菌均有效的“间隔”臂 金黄色葡萄球菌 CP 与重组假单胞菌外蛋白 A 结合。 这些疫苗表现出增强的免疫原性和 T 细胞依赖性 小鼠的特性。 此外，金黄色葡萄球菌 5 型多糖结合 重组蛋白已在第一阶段人体中成功评估 研究。