Genetic immunization against pneumococcal disease

描述(申请人提供)：肺炎链球菌是中耳炎和急性呼吸道感染最常见的细菌来源，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。目前获得许可的肺炎链球菌多糖疫苗效力低，因此有必要研究更有效的肺炎链球菌病疫苗。这项研究的长期目标是利用肺炎链球菌的遗传和抗原性保守的外膜蛋白PSPA、PSAA和解毒肺炎溶血素(PDB)开发一种针对肺炎球菌疾病的多组分疫苗。我们的假设是，一种有效的肺炎球菌疫苗应该由多个保守的相关抗原组成，最好是通过粘膜途径传递，以提供对肺炎链球菌感染的最佳非血清型依赖保护。无复制能力的腺病毒载体经鼻和经皮免疫已被证明是一种有效和简单的免疫方法。这种非侵入性的疫苗投放无疑将提高疫苗接种计划的合规性。在本项目中，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，将通过鼻腔和经皮给药的不同组合的腺病毒载体免疫方案与肌肉注射表达载体的方案进行比较。该项目的具体目标是： 具体目标1：研制一种无复制能力的腺病毒载体疫苗，以对抗肺炎链球菌。 具体目的#2：对腺病毒载体疫苗经鼻腔和经皮给药与质粒表达载体肌肉注射诱导的黏膜免疫和全身免疫进行比较。

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.