IMMUNOGENICITY OF MALARIA VACCINES IN RHESUS MACAQUES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：在启动临床试验之前，在非人类灵长类动物身上测试一种候选疟疾疫苗，以确定可能的副作用。大卫·沃特金斯博士是这个项目的领导者。 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。牛津大学的科学家们正在开发和评估各种新的方法，以提高重组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上进行的，但研究人员打算继续进行临床试验。因此，本项目的目标是用三种最佳候选疫苗接种恒河猴，这些候选疫苗是在小鼠实验中挑选出来的。在目前的非人类灵长类动物实验中，我们量化了引发的免疫反应，并寻找新出现的不良反应。 研究的三种疫苗都是基于腺病毒的疫苗系统。其中一种疫苗是由重组腺病毒(AdCh63)和重组改良安卡拉痘苗病毒(MVA)制成的，每种疫苗都含有称为Me-TRAP(与凝血酶相关黏附蛋白结合的多个表位)的疟疾抗原。第二种疫苗是由含有疟疾抗原的重组腺病毒(AdCh63-MeTRAP)和含有不同疟疾抗原的重组腺病毒(AdCh63-AMA-1)制成的。第三种疫苗是由含有疟疾抗原的重组腺病毒(AdCh63-MeTRAP)和含有Toll受体信号通路免疫佐剂蛋白的重组腺病毒(AdCh63-TRAM)制成的。 与对照疫苗(表达疟疾抗原但没有佐剂的重组腺病毒)相比，这些复合疫苗在小鼠模型中显示出更好的免疫原性。我们研究了这些腺病毒疫苗系统在非人类灵长类动物中的安全性和免疫原性。 项目进展情况：项目于2009年11月竣工。 这项研究使用了动物服务和研究服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To test a candidate malaria vaccine in non-human primates to identify possible adverse side effects before initializing clinical trials. Dr. David Watkins is the leader on this project. New vaccines are urgently needed against malaria to control the huge global mortality caused by this infectious disease. 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 recombinant viral vectored vaccines. The studies so far have been conducted in small animal models, but the investigators intend to proceed towards clinical trials. Therefore the goal of the present project was to vaccinate Rhesus macaques with three of the best vaccine candidates that were selected during experiments using mice. In the present non-human primate experiments we quantified the elicited immune responses, and were looking for emerging adverse reactions. The three vaccines that were studied were Adenovirus-based vaccine systems. One vaccine was made of a recombinant Adenovirus (AdCh63) and a recombinant Modified Vaccinia Ankara (MVA), each containing the malaria antigens called Me-TRAP (Multiple Epitopes conjugated to Thrombospondin Related Adhesion Protein). The second vaccine was made of a recombinant Adenovirus containing the malaria antigen (AdCh63-MeTRAP) and a recombinant Adenovirus containing a different malaria antigen called Apical Membrane Antigen-1 (AdCh63-AMA-1). The third vaccine was made of a recombinant Adenovirus containing the malaria antigens (AdCh63-MeTRAP) and a recombinant Adenovirus containing an immnoadjuvant protein from the Toll receptor signaling pathway called TRAM (AdCh63-TRAM). These composite vaccines show improved immunogenicity in mouse models as compared to a control vaccine (recombinant Adenovirus expressing the malaria antigen but no adjuvant). We investigated the safety and immunogenicity of these adenovirus vaccine system in non-human primates. PROJECT PROGRESS: The project was completed in November of 2009. This research used Animal Services and Research Services.