MODULAR CHIMERIC VACCINES TAILORED FOR MALARIA PARASITES

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 本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，作为控制流行地区疾病的有效干预措施。MCV是合成基因，其被设计为表达衍生自几种蛋白质和许多疟原虫通用T细胞表位的保护性抗原阵列。疟原虫的通用T细胞表位将促进辅助性T细胞应答，克服与几种疟疾抗原相关的遗传限制，并促进由自然暴露于疟原虫诱导的增强效应。MCV被设计为诱导对寄生虫生命周期的几个阶段的免疫应答。我们在严格的保护模型中对MCV进行的严格评估将为推进该疫苗平台的开发提供关键数据，以用于临床试验。相关性：由间日疟原虫引起的疟疾是一个主要的世界性健康问题，估计每年有8 000万病例。 在非洲以外，间日疟原虫是分布最广的疟疾寄生虫。间日疟原虫疟疾正在死灰复燃，现在在已经根除的地区构成严重威胁。间日疟原虫氯喹和伯氨喹耐药菌株的出现使人们越来越重视对控制这种感染的替代预防和治疗策略的需求。在此期间，利用啮齿类疟原虫约氏疟原虫进行的原理验证研究已经完成。三种嵌合蛋白被设计用于覆盖寄生虫发育的两个不同阶段，已经在小鼠中测试了其功效。在此期间，还表达和纯化了为间日疟原虫设计的另外两种MCV，并完成了初步生物学表征。这些实验为研究MCV在非人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.