IMMUNOGENICITY OF MALARIA VACCINES IN RHESUS MACAQUES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：在非人灵长类动物中测试候选疟疾疫苗，以在启动临床试验之前确定可能的不良副作用。大卫沃特金斯博士是这个项目的负责人。 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，但研究人员现在打算用这些有前途的新佐剂疫苗进行临床试验。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。因此，本项目的目标是用在小鼠实验中选择的最佳候选疫苗接种恒河猴。在目前的非人灵长类动物实验中，我们将量化引发的免疫反应，并将寻找新出现的不良反应。 每只动物将用经基因工程改造以表达融合疟疾抗原ME-TRAP（多表位-血小板反应蛋白相关粘附蛋白）的复制缺陷型腺病毒载体（AdCh 63）免疫（第0天）。至少8周后，用也表达ME-TRAP的高度减毒痘病毒（MVA）加强动物。佐剂化载体还表达衍生自人共刺激分子和细胞因子家族的分子佐剂。

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. 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 intend to proceed towards clinical trials with these promising new adjuvanted vaccines. However, before initializing clinical trials it is mandatory to test the candidate vaccines in non-human primates to identify possible adverse side effects. Therefore the goal of the present project is to vaccinate Rhesus macaques with the best vaccine candidate that was selected during experiments using mice. In the present non-human primate experiments we will quantify the elicited immune responses, and will be looking for emerging adverse reactions. Each animal will be immunized (day 0) with a replication-deficient Adenovirus vector (AdCh63) genetically engineered to express a fusion malaria antigen ME-TRAP (Multiple Epitope-Thrombospondin Related Adhesion Protein). The animals will be boosted at least 8 weeks later with a highly attenuated pox-virus (MVA) also expressing ME-TRAP. The adjuvanted vectors also express a molecular adjuvant derived from a family of human co-stimulatory molecules and cytokines.