Quantification of wild-type and radiation attenuated Plasmodium falciparum sporozoite motility in human skin

• Published in: Scientific reports Vol. 9; no. 1; pp. 13436 - 11
• Main Authors: Winkel, Béatrice M. F., de Korne, Clarize M., van Oosterom, Matthias N., Staphorst, Diego, Meijhuis, Mark, Baalbergen, Els, Ganesh, Munisha S., Dechering, Koen J., Vos, Martijn W., Chevalley-Maurel, Séverine C., Franke-Fayard, Blandine, van Leeuwen, Fijs W. B., Roestenberg, Meta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-09-2019; Nature Publishing Group
• Subjects: 14/19; 631/326/417; 692/308/2778; 692/699/255; Animals; Anopheles - parasitology; Explants; Green Fluorescent Proteins - genetics; Host-Parasite Interactions; Humanities and Social Sciences; Humans; Image processing; Image Processing, Computer-Assisted; Infectivity; Malaria; Motility; multidisciplinary; Organisms, Genetically Modified; Parasites; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - pathogenicity; Plasmodium falciparum - radiation effects; Science; Science (multidisciplinary); Skin; Skin - parasitology; Software; Sporozoites; Sporozoites - pathogenicity; Sporozoites - radiation effects; Vaccines; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49895-3

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.