Discovery of Vaccine and/or Drug Targets in Plasmodium Falciparum using Irradiated Long-Lived Merozoites

Development of a malaria vaccine, as well as, new drugs is crucial for the future control of Plasmodium falciparum, the most severe form of human malaria causing nearly a million deaths each year. Unfortunately, no licensed malaria vaccine is available and development of drug resistant parasites is a continual problem. To provide future opportunities for development, we aimed to identify the phenotypic difference(s) between a novel irradiated P. falciparum long-lived merozoite line and its parental line that displays up to a 20 fold increase in erythrocyte invasion rates, in vitro. Using the tools of systems biology, the two parasite lines were compared by Next-Gen sequencing, transcriptional analysis using microarrays and label-free quantitative proteomics (MSE) with or without ion-mobility utilizing both ProteinLynx Global SERVER™ and TransOmicsTM informatics software. Even though a limited number of changes were observed by Next-Gen sequencing andtranscriptional profiling of merozoites, significant changes in 25% of the proteins were observed in invasive merozoites with a fold change of greater than 20% by label-free quantitative proteomics. Over 100 unique proteins were quantified in the long-lived merozoites compared to 34 in the parental line. This quantitative proteomics approach for the identification of new classes of proteins involved in merozoite invasion, once qualified by independent investigations, could prove to be useful for development of new antima...
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