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（申请人提供）：肺炎链球菌（肺炎球菌）是世界范围内人类的主要病原体，引起肺部、中枢神经系统、血液和中耳的严重感染。 目前的疫苗和抗生素不能为所有年龄段的个体、所有部位的感染或针对所有菌株（血清型）的肺炎球菌提供同等或充分的保护。因此，设计一种基于相对不变的病原体编码蛋白的肺炎球菌疫苗将是有价值的，这些蛋白存在于所有或大多数菌株中并且可以引发保护性抗体。此外，能够增强这些蛋白质引发保护性抗体反应的能力也很有价值。目标 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。这一目标下的研究还将探讨宿主蛋白介导 PspA 免疫反应增强的机制。目标 2. 确定源自肺炎球菌的蛋白质 (PspA) 在与肺炎球菌荚膜多糖 (PS) 物理连接时是否比非肺炎球菌蛋白质更有效地增强 PS 特异性血清抗体反应。目标 3. 确定与正常小鼠相比，缺乏 taci 基因（参与抗 PS 抗体反应）的小鼠对肺炎球菌 PS 蛋白缀合物疫苗和肺炎球菌的反应如何。这一目标还将确定免疫或未免疫的 taci 缺陷小鼠对肺炎球菌感染的易感性是否增加。