IMMUNITY TO PNEUMOCOCCAL SURFACE PROTEIN A AND C

描述（改编自申请人的摘要）：该提案旨在 继续布里尔斯博士的研究工作， 表面抗原 该应用程序侧重于第一个细胞相关的 PspA，以及第二个新发现的蛋白质PspC。 这两种蛋白质本身可作为疫苗或作为蛋白质载体 用于荚膜多糖-蛋白质缀合物。 PspA存在于所有 肺炎球菌菌株，并可引发针对脓毒症的保护性免疫， 小鼠鼻咽部携带。 PspC与PspA相关，但在 大小，并显示在其C-末端一半具有PspA的虚拟身份。 的 拟议的研究将确定PspC是否是毒力因子， 是否能得到保护 PspA和PspC的相对作用 将检查非免疫动物的毒力和携带情况。 此外，本发明还提供了一种方法， 针对PspA和PspC的免疫在携带，脓毒症， 以及肺炎球菌从鼻咽的传播。 的 抗这些分子的人抗体保护小鼠免受感染的能力 将被评估。 PspA和PspC之间的交叉反应区域 蛋白质将被识别，以及每个分子的区域， 可用作疫苗。 将评价对PspA和PspC的抗扰度， 确定它是否涉及调理作用，阻断毒力功能，或 其他机制的行为。 获得的数据将有助于 PspA和PspC保护性免疫相关性的发展， 用于疫苗开发。

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.