Date of Award

January 2011

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

John Rose

Subject Area(s)

Medicine

Abstract

There are an estimated 300-500 million cases of malaria every year, resulting in approximately 2 million deaths. Malaria mortality occurs primarily in children under the age of five, and is resultant from the development of severe malaria. Attempts to control P. falciparum malaria face rapidly escalating levels of resistance on two fronts: the parasite to anti-malarial drugs, and the mosquito vector to insecticides. Despite current prevention efforts, the global incidence of malaria continues to rise and there is a clear and urgent need for a malaria vaccine. Malaria vaccine efforts thus far have been largely unsuccessful in eliciting robust and long-lasting immunity. While adults living in malaria endemic regions have not been shown to naturally develop protective immunity to uncomplicated malaria, they do appear to develop protective immunity to severe malaria by around the age of five, raising the possibility that a vaccine specifically targeting severe malaria may be a more attainable goal of malaria vaccine efforts in the immediate future. There is mounting evidence that the pathogenesis of severe malaria is directly related to cytoadhesion and rosetting of parasitized red blood cells. The P. falciparum protein PfEMP1, which is expressed on the surface of parasitized red blood cells, appears to have a direct role in mediating cytoadhesion and rosetting. The DBL1α domain of PfEMP1 specifically been implicated in these interactions, and is also one of the only regions of PfEMP1 that is highly conserved, making it a promising target antigen for malaria vaccine development. Here we show that immunization with recombinant vesicular stomatitis virus vaccine vectors expressing DBL1α induce immune responses that are able to disrupt rosetting of parasitized RBC. This response was comparable with that seen in adults from malaria endemic regions.

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