Pathogen and Host Proteins in Pneumococcal Immunity

描述(申请人提供)：肺炎链球菌(肺炎球菌)是一种世界性的人类主要病原体，可导致肺部、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人、所有地点的感染或所有菌株(血清型)的肺炎球菌提供同等或足够的保护。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，并能引发保护性抗体。此外，能够增强这些蛋白质诱导保护性抗体反应的能力也是有价值的。目的1.确定宿主编码的免疫系统分子BLyS和C3d是否能增强对肺炎球菌蛋白PSPA的潜在保护性免疫反应。在这一目标下的研究还将解决宿主蛋白介导对PSPA的免疫反应的任何增强的机制。目的2.确定肺炎球菌来源的蛋白(PSPA)在与肺炎球菌荚膜多糖(PS)物理连接时，在增强PS特异性血清抗体反应方面是否比非肺炎球菌蛋白更有效。目的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蛋白结合疫苗和肺炎球菌的反应如何。这一目标还将确定TACI缺陷小鼠，无论是免疫的还是未免疫的，是否增加了对肺炎球菌感染的易感性。

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.