MODULAR CHIMERIC VACCINES TAILORED FOR MALARIA PARASITES

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。 这项研究的总体重点是优化疟疾模块嵌合疫苗(MCV)的设计、组成和配方，作为在流行地区控制疾病的有效干预措施。MCV是一种合成基因，旨在表达一系列保护性抗原，这些抗原来自几种蛋白质和一些疟原虫通用T细胞表位。疟疾寄生虫的通用T细胞表位将促进辅助T细胞反应，克服与多种疟疾抗原相关的遗传限制，并促进自然暴露于疟疾寄生虫所产生的增强效应。MCV的设计目的是诱导对寄生虫生命周期的几个阶段的免疫反应。我们在严格的保护模型中对MCV的严格评估将为推动该疫苗平台的开发用于临床试验提供关键数据。相关性：由间日疟原虫引起的疟疾是一个重大的世界性健康问题，估计每年有8000万病例。 在非洲以外，间日疟原虫是分布最广的疟疾寄生虫。间日疟正在死灰复燃，在已经根除的地区，它现在是一个严重的威胁。间日疟原虫、氯喹和伯氨喹抗药性菌株的出现使人们更加强调需要有替代的预防和治疗策略来控制这种感染。在此期间，利用啮齿动物疟疾寄生虫P.yoelii进行的原理研究的证据已经完成。设计用于覆盖寄生虫发育的两个不同阶段的三种嵌合蛋白已经在小鼠身上进行了有效性测试。在此期间，还表达和纯化了另外两个为间日疟原虫设计的MCV，并完成了初步的生物学特性。这些实验为研究MCV在非人类灵长类疟疾模型中的疫苗效力开辟了道路。

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. The overall focus of this research has been to optimize the design, composition and formulation of malaria Modular Chimeric Vaccines (MCVs) as effective intervention measures to control the disease in endemic areas. MCVs are synthetic genes designed to express an array of protective antigens derived from several proteins and a number of Plasmodium universal T cell epitopes. Malaria parasites' universal T cell epitopes will promote helper T-cell responses, overcome the genetic restriction associated with several malaria antigens and facilitate the boosting effect induced by natural exposure to malaria parasites. MCVs are designed to induce immune responses to several stages of the parasite life cycle. Our rigorous evaluation of MCVs in stringent models of protection will provide critical data to advance the development of this vaccine platform for use in clinical trials. Relevance: malaria caused by P. vivax is a major worldwide health problem with an estimated 80 million cases annually. Outside Africa, P. vivax is the most widely distributed malaria parasite. P. vivax malaria is resurging and now represents a serious threat in areas where it had been eradicated. The emergence of P. vivax chloroquine and primaquine drug resistant strains has brought increased emphasis to the need for alternative prophylactic and therapeutic strategies to control this infection. During this period proof of principle studies, using the rodent malaria parasite P. yoelii, have been completed. Three chimeric proteins designed to cover two different stages of the parasite development have been tested for efficacy in mice. Two additional MCVs designed for P. vivax have been also expressed and purified during this period and preliminary biological characterization has been completed. These experiments open the way to study vaccine efficacy of MCVs in non-human primate models of malaria.