IMMUNITY TO PNEUMOCOCCAL SURFACE PROTEIN A AND C

描述(改编自申请人的摘要)：该提案旨在 在继续Briles博士在肺炎球菌研究方面的努力 表面抗原。该应用程序主要关注与第一个单元格相关联的 描述的蛋白质，PSPA，以及第二个新发现的蛋白质，PSPC。 这两种蛋白质既可以作为疫苗本身，也可以作为蛋白质载体。 用于胶囊多糖-蛋白质结合物。PSPA存在于所有 肺炎球菌菌株，可诱导对脓毒症的保护性免疫 小鼠的鼻咽部携带。PSPC与PSPA相关，但在 大小，并在其C-末端半部分显示与PSPA的虚拟身份。这个 拟议的研究将确定PSPC是否是一个毒力因素和 它是否能获得保护。PSPA和PSPC在人类免疫系统中的相对作用 将检查非免疫动物的毒力和携带情况。此外, 针对PSPA和PSPC的免疫在携带性、败血症、 并将探索肺炎球菌从鼻咽传播的情况。这个 人抗这些分子抗体保护小鼠免受感染的能力 将会被评估。PSPA和PSPC之间的交叉反应区 将识别蛋白质以及每个分子的大部分区域 作为疫苗很有用。对PSPA和PSPC的免疫力将评估为 确定它是否涉及调理作用、阻断毒力功能或 由其他机制采取行动。所获得的数据将有助于 PSPA和PSPC保护性免疫相关基因的研究进展 应用于疫苗研发。

DESCRIPTION (Adapted from the applicant's abstract): The proposal is aimed at continuing Dr. Briles' research efforts in the study of pneumococcal surface antigens. The application focuses on the first cell-associated protein described, PspA, as well as a second newly discovered protein, PspC. These two proteins may serve as vaccines themselves or as protein carriers for capsular polysaccharide-protein conjugates. PspA is present on all pneumococcal strains and can elicit protective immunity against sepsis and nasopharyngeal carriage in mice. PspC is related to PspA, but larger in size, and shows virtual identity with PspA in its C-terminal half. The proposed studies will determine whether PspC is a virulence factor and whether it can elicit protection. The relative roles of PspA and PspC in virulence and carriage in nonimmune animals will be examined. In addition, the relative roles of immunity against PspA and PspC in carriage, sepsis, and spread of pneumococci from the nasopharynx will be explored. The ability of human antibody to these molecules to protect mice from infection will be evaluated. Cross-reactive regions between the PspA and PspC proteins will be identified as well as the regions of each molecule most useful as a vaccine. Immunity to PspA and PspC will be evaluated to determine whether it involves opsonization, blocks virulence functions, or acts by other mechanisms. The data obtained will assist with the development of correlates of protective immunity for PspA and PspC that can be applied to vaccine development.