Generating a novel dual stage malaria vaccine

项目概要/摘要 疟疾是由疟原虫寄生虫感染引起的，是一个重大的全球健康问题，需要长期的治疗。 有效疫苗。RTS，S是自20世纪80年代以来开发的唯一获得许可的疟疾疫苗， 疟原虫生命周期的无症状肝脏阶段。然而，RTS，S仅提供低水平的初始 保护，在最初几年显着减弱，此时患者不再受到保护 有症状的血液阶段疟疾感染。因此，非常需要改进的疟疾疫苗。 我们最近发表的研究表明，在肝脏中存活的疟原虫 感染阶段和进入血液感染阶段可以诱导炎症环境， 对肝脏阶段寄生虫的持续免疫反应。因此，我们假设开发一种疫苗， 靶向肝脏和血液阶段寄生虫将防止肝脏阶段免疫应答的破坏 是由血液阶段的炎症引起的如果我们的假设是正确的，双阶段免疫将导致两个 除了增强肝脏阶段免疫外，还增加了抗原靶点的宽度。这项提案的目的是 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颗粒疫苗和转基因疫苗组成的系统。 疟原虫，以推动免疫保护的极限，并获得更好的理解， 疫苗方案。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， 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.