Genetic immunization against pneumococcal disease

描述（由申请人提供）：肺炎链球菌是中耳炎和急性呼吸道感染的最常见细菌性病因，据估计，每年全球有超过300万儿童死于侵袭性疾病，如肺炎、菌血症、脑膜炎和败血症。目前许可的肺炎球菌多糖疫苗的低效力使得有必要研究针对肺炎球菌疾病的更有效的疫苗。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，使用来自S.肺炎。我们的假设是，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，以提供针对S的最佳非血清型依赖性保护。肺炎感染。鼻内和经皮免疫与复制缺陷型腺病毒载体已被证明是有效和简单的免疫。这种非侵入性疫苗输送无疑将提高疫苗接种计划的依从性。本课题将构建编码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，将通过鼻内和经皮递送模式使用腺病毒载体的不同组合的免疫方案与质粒表达载体的肌内注射进行比较。该项目的具体目标是： 具体目标#1：开发针对肺炎链球菌的无复制能力的腺病毒载体疫苗。 具体目标#2：比较腺病毒载体疫苗经鼻和经皮给药与质粒表达载体经肌肉注射诱导的粘膜和全身免疫。

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.