Generating a novel dual stage malaria vaccine

项目摘要/摘要 疟疾是由疟原虫感染引起的，是一个需要长期持续的重大全球健康问题。 有效的疫苗。自20世纪80年代以来一直在研发，S是唯一获得许可的疟疾疫苗，目标是 疟原虫生命周期中的无症状肝脏阶段。然而，RTS，S只提供了低水平的初始 保护，这种保护在最初的几年里显著减弱，此时患者不再受到保护 来自有症状的血液期疟疾感染。因此，迫切需要一种改进的疟疾疫苗。 我们最近发表的研究表明，存活在肝脏中的疟原虫 感染阶段和进入血液感染阶段会引发炎症环境，破坏 对肝期寄生虫的持续免疫反应。因此，我们假设研发一种疫苗 针对肝脏和血液阶段的寄生虫将防止破坏肝脏阶段的免疫反应 由血液期炎症引起。如果我们的假设是正确的，两阶段免疫将导致 除了增强肝期免疫外，还增加了抗原靶向的广度。这项提案的目标是 是开发一种动物模型系统，使我们能够测试这种疫苗的保护能力 人类。我们建议开发一种由新型纳米疫苗和转基因疫苗组成的系统 推动疟原虫免疫保护极限，更好地了解最优 疫苗接种方案。我们已经组建了一支理想的团队，他们拥有知识和技术专长来 实现这一目标。

Project Summary/Abstract Malaria, caused by infection with Plasmodium parasites, is a major global health issue in need of a long lasting effective vaccine. In development since the 1980s, RTS,S is the only licensed malaria vaccine and targets the asymptomatic liver stage of the Plasmodium life cycle. However, RTS,S offers only low levels of initial protection, which wane significantly over the first few years, at which point patients are no longer protected from symptomatic blood stage malaria infection. Hence, there is a great need for an improved malaria vaccine. We have recently published studies demonstrating that Plasmodium parasites that have survived the liver infective stage and entered the blood infective stage can induce an inflammatory environment that disrupts the ongoing immune response to liver stage parasites. Therefore, we hypothesize that developing a vaccine that targets both liver and blood stage parasites will prevent the disruption of the liver stage immune response caused by the blood stage inflammation. If our hypothesis is correct, dual stage immunization will result in both increased breadth of antigenic targets in addition to enhancing liver stage immunity. The goal of this proposal is to develop an animal model system that will allow us to test the protective capacity of such a vaccine for humans. We propose to develop a system consisting of novel nanoparticle vaccines and transgenic Plasmodium parasites to push the limits of immune protection and gain a better understanding of optimal vaccine regimens. We have assembled the ideal team that has the knowledge and technical expertise to realize this goal.