IMMUNOGENICITY OF IMPROVED MALARIA VACCINES IN RHESUS MACAQUES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目标：用在小鼠实验中选择的三种最佳候选疫苗接种恒河猴，并量化引发的免疫应答，以寻找新出现的不良反应。 迫切需要针对疟疾的新疫苗，以控制这种传染病造成的巨大全球死亡率。许多领先的候选疫苗包括来自这些微生物的基因，作为称为载体的减毒病毒的一部分。然而，如果这些疫苗要获得广泛成功，载体疫苗需要诱导强免疫力。牛津大学的科学家们正在开发和评估各种新方法，以提高这种病毒载体疫苗产生的免疫反应的强度。到目前为止，这些研究都是在小动物模型中进行的，但研究人员现在将对这些有前途的新疫苗进行临床试验。然而，在启动临床试验之前，必须在非人灵长类动物中测试候选疫苗，以确定可能的不良副作用。 进展： 牛津大学的科学家们已经开发出三种基于腺病毒的疫苗系统来免疫疟疾抗原。一种疫苗方案由重组腺病毒（AdCh 63）和重组修饰的安卡拉牛痘（MVA）制成，每种都含有与血小板反应蛋白相关粘附蛋白（Me-TRAP）缀合的疟疾抗原多表位。第二种疫苗方案由含有与血小板反应蛋白相关粘附蛋白缀合的疟疾抗原多表位（Me-TRAP）的重组腺病毒、含有称为4-1BBL的免疫刺激性抗原的重组腺病毒（AdCh 63 -4-1BBL）和含有疟疾和免疫刺激性抗原两者的修饰的安卡拉牛痘（MVA）（MVA-MeTRAP-4-1BBL）制成。第三种疫苗方案由重组腺病毒和重组MVA组成，所述重组腺病毒含有与免疫刺激蛋白IMX 313缀合的与血小板反应蛋白相关粘附蛋白缀合的修饰的疟疾抗原多表位，所述重组MVA含有与免疫刺激蛋白IMX 313缀合的与血小板反应蛋白相关粘附蛋白缀合的修饰的疟疾抗原多表位。与对照疫苗（表达疟疾抗原的重组腺病毒，无免疫刺激蛋白）相比，这些复合疫苗在小鼠模型中显示出改善的免疫原性。我们研究了这些腺病毒疫苗系统在非人灵长类动物中的安全性和免疫原性。我们在2010年11月底完成了这些实验。 这项研究使用了动物服务，CPI和免疫学服务。 出版物： 没有。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To vaccinate Rhesus macaques with three of the best vaccine candidates selected during experiments using mice and quantify the elicited immune responses to look for emerging adverse reactions. New vaccines are urgently needed against malaria to control the huge global mortality caused by this infectious disease. Many leading candidate vaccines include a gene from these microbes as part of an attenuated virus known as a vector. Vectored vaccines, however, will need to induce strong immunity if these vaccines are to be widely successful. Scientists at the University of Oxford are developing and assessing a variety of novel approaches to improving the strength of the immune responses produced by such viral vectored vaccines. The studies so far have been conducted in small animal models, but the investigators will now proceed towards clinical trials with these promising new vaccines. However, before initializing clinical trials it is mandatory to test the candidate vaccines in non-human primates to identify possible adverse side effects. PROGRESS: Scientists at the University of Oxford had developed three Adenovirus-based vaccine systems to immunize against malaria antigens. One vaccine regimen was made of a recombinant Adenovirus (AdCh63) and a recombinant Modified Vaccinia Ankara (MVA), each containing the malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein (Me-TRAP). The second vaccine regimen was made of a recombinant Adenovirus containing the malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein (Me-TRAP), a recombinant Adenovirus containing an immunostimulatory antigen called 4-1BBL (AdCh63-4-1BBL) and a Modified Vaccinia Ankara (MVA) containing both the malaria and the immunostimulatory antigens (MVA-MeTRAP-4-1BBL). The third vaccine regimen was made of a recombinant Adenovirus containing the modified malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein conjugated to an immunostimulatory protein IMX313 and a recombinant MVA containing the modified malaria antigens Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein conjugated to an immunostimulatory protein IMX313. These composite vaccines had shown improved immunogenicity in mouse models as compared to a control vaccine (recombinant Adenovirus expressing the malaria antigen no immunostimulatory proteins). We investigated the safety and immunogenicity of these Adenovirus vaccine systems in non-human primates. We finished these experiments at the end of November 2010. This research used Animal Services, CPI and Immunology Services. PUBLICATIONS: None.