Generating a novel dual stage malaria vaccine

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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.