Clustering and erratic movement patterns of syringe-injected versus mosquito-inoculated malaria sporozoites underlie decreased infectivity

Abstract

Live attenuated malaria sporozoites are promising vaccine candidates, however, their efficacy critically depends on their capability to reach and infect the host liver. Administration via mosquito inoculation is by far the most potent method for inducing immunity, but highly unpractical. Here, we observed that intradermal syringe-injected Plasmodium berghei sporozoites (syrSPZ) were three-fold less efficient in migrating to and infecting mouse liver compared to mosquito-inoculated sporozoites (msqSPZ). This was related to a clustered dermal distribution (2-fold decreased median distance between syrSPZ vs msqSPZ) 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 pressure 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.

Sporozoite motility as a quantitative readout for anti-CSP antibody inhibition

“…SPZ are considered an attractive vaccine target, since this early life cycle stage is the longest extracellular stage of the life cycle (ranging from minutes to hours 7,8 ). This stage also presents a bottleneck for the infection process as approximately only 1-500 SPZ are inoculated by a mosquito 9,10 . CSP is thought to play a critical role in SPZ migration; an essential process which enables the SPZ to migrate from the inoculation site to the liver and invade hepatocytes to establish a full-blown infection 11,12 .…”