To IMAGE or to IMAGINE: visualization of parasite migration as a means to support (malaria) parasite vaccine development

Korne, C.M. de (2023)

Doctoral Thesis

This thesis presents the development of quantitative imaging tools to study parasite migration. Since migration is crucial for malaria parasites to continue their life cycle, factors influencing their migration capability may also impact the efficacy of malaria vaccine candidates. Here, imaging of parasite migration was used to gain insights that can support the development of antiparasitic vaccines. SMOOT (Sporozoite Motility Orienting and Organizing Tool) was developed and established as a quantitative software analysis tool for tracking the migration of malaria sporozoites in vitro and in human skin explant. This tool provides a readout with high kinematic detail, enabling the quantitative characterization of novel factors influencing the migration capability of malaria sporozoites. Subsequently, the study of sporozoite migration was expanded beyond in vitro and ex vivo models. A hybrid tracer labeling approach for malaria sporozoites was developed and used to reveal the in vivo dissemination of malaria sporozoites in a murine model. This multimodal imaging approach was also applied to investigate human skin invasion by helminth larvae. This thesis concludes with a review of the broader potential for imaging technology to advance the development of new diagnostic methods, therapeutic interventions and vaccines for combating parasitic infections.

• Quantitative imaging
• In vivo tracking
• Parasite migration
• Sporozoite motility
• Malaria
• Schistosoma mansoni
• Necator americanus
• Hybrid tracer
• Vaccine development

• All authors: Korne, C.M. de
• Supervisor: Leeuwen, F.W.B. van; Roestenberg, M.
• Committee: Kroes, A.C.M.; Smits, H.H.; Oosterom, M.N. van; Velders, A.H.; Hellemond, J.J. van
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2023-11-02