Pathogen and Host Proteins in Pneumococcal Immunity

肺炎球菌免疫中的病原体和宿主蛋白

• 批准号: 6681718
• 负责人: NEIL S GREENSPAN
• 金额: $ 34.43万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681718
• 关键词: SDS polyacrylamide gel electrophoresis; Streptococcus pneumoniae; antibacterial antibody; autoimmunity; bacterial polysaccharides; bacterial proteins; bacterial vaccines; bactericidal immunity; cellular immunity; chimeric proteins; clinical research; cytokine receptors; enzyme linked immunosorbent assay; host organism interaction; human subject; immunization; immunoconjugates; immunogenetics; immunomodulators; laboratory mouse; recombinant proteins; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Streptococcus pneumoniae (pneumococcus) is a major worldwide pathogen of humans, causing serious infections in the lungs, central nervous system, blood, and middle ear. Current vaccines and antibiotics do not provide equal or adequate protection for individuals of all ages, infections at all sites, or against pneumococci of all strains (serotypes). Therefore, it would be valuable to devise a pneumococcal vaccine based on relatively invariant pathogen-encoded proteins that are present in all or most strains and that can elicit protective antibodies. In addition, it would be valuable to be able to augment the abilities of these proteins to elicit protective antibody responses. Aim 1. To determine if the host-encoded immune system molecules, BLyS and C3d, can enhance potentially protective immune responses to the pneumococcal protein PspA. Studies under this aim will also address the mechanisms by which host proteins mediate any enhancements of the immune responses to PspA. Aim 2. To determine if a protein derived from the pneumococcus (PspA) can be more effective than a non-pneumococcal protein, when physically linked to pneumococcal capsular polysaccharides (PS), at enhancing the PS-specific serum antibody response. Aim 3. To determine how, in comparison to normal mice, mice lacking the taci gene (involved in anti-PS antibody responses) respond to pneumococcal PS-protein conjugate vaccines and to pneumococci. This aim will also determine if taci-deficient mice, immunized or unimmunized, have increased susceptibility to pneumococcal infection.

描述（由申请人提供）：肺炎链球菌（肺炎球菌）是人类的主要病原体，在肺，中枢神经系统，血液和中耳引起严重的感染。 当前的疫苗和抗生素不能为所有年龄的个体，所有部位感染或针对所有菌株的肺炎球（血清型）提供相等或适当的保护。因此，基于相对不变的病原体编码的蛋白质，在所有或大多数菌株中都具有相对不变的病原体编码蛋白，并且可以引起保护性抗体。此外，能够增强这些蛋白质引起保护性抗体反应的能力是有价值的。目的1。确定宿主编码的免疫系统分子，Blys和C3D是否可以增强对肺炎球菌蛋白PSPA的潜在保护性免疫反应。该目标下的研究还将解决宿主蛋白介导对PSPA免疫反应的任何增强的机制。目的2。确定源自肺炎球菌（PSPA）的蛋白质是否比非肺炎球菌蛋白更有效，而与肺炎球菌囊囊多糖（PS）相关时，是否可以增强PS PS特异性血清抗体抗体响应。目的3。为了确定与正常小鼠相比，缺乏TACI基因（参与抗PS抗体反应）的小鼠如何应对肺炎球菌PS-蛋白结合疫苗和肺炎球。该目标还将确定缺乏TACI的小鼠免疫或未免疫的小鼠对肺炎球菌感染的敏感性增加。