Genetic immunization against pneumococcal disease

描述（由申请人提供）：肺炎链球菌是引起中耳炎和急性呼吸道感染的最常见细菌，据估计，每年全世界有300多万儿童死于肺炎、菌血症、脑膜炎和败血症等侵袭性疾病。目前已获批的肺炎球菌多糖疫苗效力较低，因此有必要研究更有效的肺炎球菌疫苗。本研究的长期目标是开发一种针对肺炎球菌疾病的多组分疫苗，利用遗传和抗原保守的外膜蛋白PspA、PsaA和来自肺炎链球菌的解毒溶肺素（PdB）。我们的假设是，一种有效的肺炎球菌疫苗应该由多种保守的相关抗原组成，最好通过粘膜途径递送，以提供最佳的非血清型依赖的保护，防止肺炎链球菌感染。鼻内和经皮免疫复制无能腺病毒载体已被证明是有效和简单的免疫接种。这种非侵入性的疫苗递送无疑将提高疫苗接种计划的依从性。本项目将构建编码PspA、PsaA和PdB的腺病毒和质粒表达载体。为了获得最佳的疫苗接种方案，将不同的腺病毒载体组合通过鼻内和经皮递送方式与肌内注射质粒表达载体进行比较。该项目的具体目标是：

DESCRIPTION (provided by applicant): Streptococcus pneumoniae is the most common bacterial cause of otitis media and acute respiratory infection and is estimated to result in over three million deaths in children every year worldwide from invasive diseases such as pneumonia, bacteremia, meningitis, and septicemia. The low efficacy of currently licensed pneumococcal polysaccharide vaccine has necessitated research into more efficient vaccines against pneumococcal disease. The long-term goal of this research is to develop a multi-component vaccine against pneumococcal disease, using genetically and antigenically conserved outer membrane proteins PspA, PsaA, and detoxified pneumolysin (PdB) from S. pneumoniae. Our hypothesis is that an effective pneumococcal vaccine should be composed of multiple conserved relevant antigens delivered preferably by a mucosal route in order to provide the best non-serotype-dependent protection against S. pneumoniae infection. Intranasal and transcutaneous immunization with replication-incompetent adenoviral vectors have proved to be efficient and simple for immunization. This non-invasive vaccine delivery will undoubtedly enhance the compliance of a vaccination program. In this project, adenovirus and plasmid expression vectors encoding PspA, PsaA and PdB will be constructed. In order to obtain an optimal vaccination protocol, immunization regimens with different combinations of adenoviral vectors through the intranasal and transcutaneous delivery modes will be compared with the intramuscular injection of plasmid expression vectors. The specific aims of this project are: Specific Aim#1: To develop a replication-incompetent adenovirus-vectored vaccine against Streptococcus pneurnoniae. Specific Aim #2: To compare the mucosal and systemic immunity elicited by adenovirus-vectored vaccine through intranasal and transcutaneous administrations with that elicited by plasmid expression vectors through intramuscular injection.