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: 3878145
• 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/3878145
• 关键词: Cryptococcus neoformans; Haemophilus influenzae; Haemophilus influenzae vaccines; Neisseria meningitidis; Neisseria meningitidis vaccine; Pseudomonas aeruginosa; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pneumoniae vaccine; Streptococcus vaccine; antibacterial antibody; bacterial antigens; bacterial capsules; bacterial polysaccharides; bactericidal immunity; child (0-11); drug adverse effect; exotoxins; fungal vaccines; human age group; human subject; immunization; immunoconjugates; immunoglobulins; immunological substance; infant human (0-1 year); laboratory mouse; tetanus toxoid

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.

嗜血杆菌的年龄相关和T细胞非依赖性免疫学特性 流感病毒B型荚膜多糖和其它多糖 侵入性细菌限制了它们作为婴儿疫苗的保护作用， 儿童是发病率最高的年龄组， 这些病原体。一个通用的有机合成方案，可以结合H。 B型流感病毒和其它荚膜多糖与载体蛋白的结合 的免疫原性， T细胞对这些保护性抗原的依赖性（增强效应）。基于 我们和其他人的工作，一个结合的Hib疫苗，由我们的 最初的方法是由FDA批准的，可普遍用于儿童 年龄超过18个月。现在，许可证已扩展到其他 结合物和这些新产品的上市后监测成功 将年龄限制降低到15个月大。我们已经证明，我们的H。 B型流感病毒-破伤风类毒素结合物是安全和免疫原性的， 3、5、7和18个月大的婴儿（ 婴儿疫苗）。大约75%的婴儿发展出保护水平， 第三次注射后，所有人都受到了保护 注射对载体诱导保护性水平的抗体 蛋白质也是。该技术已扩展到链球菌组B III型为新型隐球菌和B群荚膜脑膜炎球菌 迄今为止，多糖被认为是非免疫原性的。高 这种结合物诱导了针对这种聚合物的抗体水平， 小鼠在成人中评价的两批肺炎球菌12型F-DT结合物 志愿者被发现是安全的，并诱导更高水平的12F型 与未结合的CP疫苗相比，用更高的 MW CP诱导更高的抗体水平。5型葡萄球菌结合物 或8与铜绿假单胞菌外毒素A的免疫原性增强 和小鼠的T细胞依赖性。