Schistosomiasis vaccine development: update on human clinical trials

Abstract

Schistosomiasis causes significant levels of morbidity and mortality in many geographical regions of the world. The disease is caused by infections with parasitic blood flukes known as schistosomes. The control of schistosomiasis over the last several decades has been centered on the mass drug administration (MDA) of praziquantel (PZQ), which is the only drug currently available for treatment. Despite the concerted efforts of MDA programs, the prevalence and transmission of schistosomiasis has remained largely unchecked due to the fact that PZQ is ineffective against juvenile schistosomes, does not prevent re-infection and the emergence of PZQ-resistant parasites. In addition, other measures such as the water, sanitation and hygiene programs and snail intermediate hosts control have had little to no impact. These drawbacks indicate that the current control strategies are severely inadequate at interrupting transmission and therefore, implementation of other control strategies are required. Ideally, an efficient vaccine is what is needed for long term protection thereby eliminating the current efforts of repeated mass drug administration. However, the general consensus in the field is that the integration of a viable vaccine with MDA and other control measures offer the best chance of achieving the goal of schistosomiasis elimination. This review focuses on the present status of schistosomiasis vaccine candidates in different phases of human clinical trials and provide some insight into future vaccine discovery and design.

Keywords: Clinical trials; Control strategies; Mass drug administration (MDA); Neglected tropical disease; Schistosomiasis; Schistosomiasis vaccine development.

Fig. 1

Life cycle of schistosomes. Five of the species of schistosome that infect humans are depicted. Infection occurs upon contact with fresh water contaminated with the free-swimming larvae known as cercariae. Cercariae penetrates the skin of humans and/or other mammalian hosts, shed their tails and transform into migrating larvae which enter into circulation traversing various host organs en route to the lungs. After many days, the worms exit the lungs and migrate to the veins of the portal system where they mature into adult male and female worms and form pairs. Worm pairs then migrate to the either the superior mesenteric veins (Schistosoma mansoni) inferior mesenteric and superior hemorrhoidal veins (S. japonicum), or the vesical plexus and veins draining the ureters (S. haematobium). Oviposition begins approximately 4–6 weeks post infection and continues throughout the lifespan of the worm. Some of the eggs laid pass from the lumen of blood vessels into various host tissues in close proximity while the remaining eggs pass through the intestinal wall or bladder and are released into the environment in feces (S. mansoni and S. japonicum) or urine (S. haematobium). Upon contact with water, the released eggs hatch into motile miracidia, which in turn, infect specific fresh water intermediate snail host depending on the species. S. mansoni infects Biomphalaria species while S. haematobium infects Bulinus species and S. japonicum infects Oncomelania species. Within the snail host, the larvae undergo a series of asexual reproduction and develop into sporocysts. Upon exposure to sunlight, ceracariae are released into fresh water to infect suitable mammalian hosts. Figure obtained from Gray DJ et al. [8] and used with permission