Gene expression profiling approach towards enhancement of malaria vaccine development

Malaria continues to be one of the highest morbidity and mortality infectious diseases in the world, posing an enormous public health burden with significant economic consequences. The development of vaccines that provide sterile protection against pathogenic infection by the Plasmodium parasites that cause malaria is thus a major global public health priority. This dissertation describes three gene expression profiling experiments using RNA sequencing technology (RNASeq) applied to samples collected during clinical trials performed at the CAUCASECO research center in Cali, Colombia. In each case, peripheral blood samples from volunteers and patients enrolled in studies addressing different aspects of immunity against P. vivax malaria were studied, namely the effect of prior exposure, the efficacy of an attenuated parasite vaccine, and resolution of complicated disease. The results presented explore how gene expression profiling of the complex mixture of cells present in whole blood can nevertheless reveal the cellular nature and duration of the immune response to P. vivax infection, while also highlighting subsets of genes that may mediate adaptive immunity. These results demonstrate the potential value of RNASeq for studying the response of the host transcriptome of a malaria infection, and represent a step toward genomic profiling as a component of personalized clinical diagnostics for malaria treatment.Ph.D