Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites.

摘要: Experimental immunization with radiation attenuated sporozoites (RAS) and genetically has proved to be a promising approach for malaria vaccine development. However, parasite biomarkers of growth attenuation enhanced immune protection in response remain poorly understood. Here, we report on the effect an attenuating dose γ-irradiation (15 krad) Plasmodium falciparum sporozoite (PfSPZ) ultrastructure by electron microscopy, rate liver stage P. cell cultures, genome-wide transcriptional profile parasites microarray. We find that treated PfSPZ retained normal cellular structure except they were vacuous partially disrupted plasma membrane inner complex. A similar infection was observed γ-irradiation-treated untreated human HCO-4 cells (0.47% versus 0.49%, respectively) day 3 post-infection. In microarray studies, cumulatively, 180 genes significantly transcriptionally altered and/or 6 Among biomarkers, identified signature seven candidate associated functionally diverse pathways may regulate induced cycle arrest within hepatocyte. repertoire 14 protein translation is overexpressed radiation. Additionally, 37 encode proteins expressed surface or exported into host cell, 4 transporters, 10 related misfolding stress-related processing. These results have increased novel targets 1) safety define proper attenuation, 2) generating candidates, 3) subunit vaccines against malaria.