1. Clustering and Erratic Movement Patterns of Syringe-Injected versus Mosquito-Inoculated Malaria Sporozoites Underlie Decreased Infectivity.
- Author
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de Korne CM, Winkel BMF, van Oosterom MN, Chevalley-Maurel S, Houwing HM, Sijtsma JC, Azargoshasb S, Baalbergen E, Franke-Fayard BMD, van Leeuwen FWB, and Roestenberg M
- Subjects
- Animals, Drug Delivery Systems, Female, Liver parasitology, Malaria prevention & control, Malaria Vaccines administration & dosage, Mice, Movement, Vaccines, Attenuated administration & dosage, Culicidae parasitology, Injections, Intradermal methods, Insect Bites and Stings parasitology, Plasmodium berghei physiology, Sporozoites physiology, Syringes
- Abstract
Malaria vaccine candidates based on live, attenuated sporozoites have led to high levels of protection. However, their efficacy critically depends on the sporozoites' ability to reach and infect the host liver. Administration via mosquito inoculation is by far the most potent method for inducing immunity but highly impractical. Here, we observed that intradermal syringe-injected Plasmodium berghei sporozoites (
syr SPZ) were 3-fold less efficient in migrating to and infecting mouse liver than mosquito-inoculated sporozoites (msq SPZ). This was related to a clustered dermal distribution (2-fold-decreased median distance betweensyr SPZ andmsq SPZ) and, more importantly, a 1.4-fold (significantly)-slower and more erratic movement pattern. These erratic movement patterns were likely caused by alteration of dermal tissue morphology (>15-μm intercellular gaps) due to injection of fluid and may critically decrease sporozoite infectivity. These results suggest that novel microvolume-based administration technologies hold promise for replicating the success of mosquito-inoculated live, attenuated sporozoite vaccines. IMPORTANCE Malaria still causes a major burden on global health and the economy. The efficacy of live, attenuated malaria sporozoites as vaccine candidates critically depends on their ability to migrate to and infect the host liver. This work sheds light on the effect of different administration routes on sporozoite migration. We show that the delivery of sporozoites via mosquito inoculation is more efficient than syringe injection; however, this route of administration is highly impractical for vaccine purposes. Using confocal microscopy and automated imaging software, we demonstrate that syringe-injected sporozoites do cluster, move more slowly, and display more erratic movement due to alterations in tissue morphology. These findings indicate that microneedle-based engineering solutions hold promise for replicating the success of mosquito-inoculated live, attenuated sporozoite vaccines., (Copyright © 2021 de Korne et al.)- Published
- 2021
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