Abstract
Given the number of global malaria cases and deaths, the need for a vaccine against Plasmodium falciparum (Pf) remains pressing. Administration of live, radiation-attenuated Pf sporozoites can fully protect malaria-naïve individuals. Despite the fact that motility of these attenuated parasites is key to their infectivity and ultimately protective efficacy, sporozoite motility in human tissue (e.g. skin) remains wholly uncharacterized to date. We show that the ability to quantitatively address the complexity of sporozoite motility in human tissue provides an additional tool in the development of attenuated sporozoite vaccines. We imaged Pf movement in the skin of its natural host and compared wild-type and radiation-attenuated GFP-expressing Pf sporozoites. Using custom image analysis software and human skin explants we were able to quantitatively study their key motility features. This head-to-head comparison revealed that radiation attenuation impaired the capacity of sporozoites to vary their movement angle, velocity and direction, promoting less refined movement patterns. Understanding and overcoming these changes in motility will contribute to the development of an efficacious attenuated parasite malaria vaccine.
Highlights
Half the human population lives in areas with an increased risk of malaria transmission, resulting in more than 200 million cases each year[1], illustrating the urgent need for a highly effective malaria vaccine
We found that Plasmodium falciparum (Pf) radiation attenuation (RA) display increased circular motility patterns, more extreme straightness index (SI) values and higher angular dispersion (AD) compared to Pf WT
Pf RA exhibit less variability in velocity over the course of their track and “reversal” patterns were unique to this group
Summary
Half the human population lives in areas with an increased risk of malaria transmission, resulting in more than 200 million cases each year[1], illustrating the urgent need for a highly effective malaria vaccine. The pioneering literature that presents image analysis of rodent sporozoite (Pb) movement in murine tissue, has focused on an often used measure of random diffusion of particles, the mean squared displacement (MSD)[9,10,28]. This measurement separates anomalous diffusion (with a non-linear relation to time), from the classic linear diffusion process. We reasoned that the concept of directional movement could complement the diffusion-based in skin sporozoite analysis and could provide a more detailed insight in sporozoite motility in complex environments such as human skin tissue
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