Abstract
Schistosomiasis is a neglected tropical disease caused by parasitic blood flukes of the genus Schistosoma, which kills 300,000 people every year in developing countries, and there is no vaccine. Recently, we have shown that cholinesterases (ChEs)—enzymes that regulate neurotransmission—from Schistosoma mansoni are expressed on the outer tegument surface and present in the excretory/secretory products of larval schistosomula and adult worms, and are essential for parasite survival in the definitive host, highlighting their utility as potential schistosomiasis vaccine targets. When treated in vitro with anti-schistosome cholinesterase (SmChE) IgG, both schistosomula and adult worms displayed significantly decreased ChE activity, which eventually resulted in parasite death. Vaccination with individual SmChEs, or a combination of all three SmChEs, significantly reduced worm burdens in two independent trials compared to controls. Average adult worm numbers and liver egg burdens were significantly decreased for all vaccinated mice across both trials, with values of 29–39% and 13–46%, respectively, except for those vaccinated with SmAChE1 in trial 1. Egg viability, as determined by egg hatching from liver homogenates, was significantly reduced in the groups vaccinated with the SmChE cocktail (40%) and SmAChE2 (46%). Furthermore, surviving worms from each vaccinated group were significantly stunted and depleted of glycogen stores, compared to controls. These results suggest that SmChEs could be incorporated into a vaccine against schistosomiasis to reduce the pathology and transmission of this debilitating disease.
Highlights
Schistosomiasis is caused by an infection with parasitic blood flukes of the genus Schistosoma, killing 300,000 people every year and infecting hundreds of millions more in developing countries [1].The disease is spread when humans come into contact with the water-borne, infective stage of the parasite—the cercariae—which penetrate the skin and migrate through the vasculature and lungs before entering the venous system, where they become sexually mature adults that pair and mate.Eggs laid by the female are passed in the urine or feces to the environment, which continues the transmission of schistosomiasis [1]
To determine the ability of anti-schistosome cholinesterase (SmChE)-specific polyclonal antibodies to inhibit ChE activity in S. mansoni, and the effect this had on parasite viability, we studied the effects of paralog-specific antibodies on schistosomula at two different timepoints
There was no correlation between pre-challenge titers and are promising candidates, as we have shown in previous immunolocalization studies of S. mansoni worm burdens in any groups
Summary
Schistosomiasis is caused by an infection with parasitic blood flukes of the genus Schistosoma, killing 300,000 people every year and infecting hundreds of millions more in developing countries [1]. Eggs laid by the female are passed in the urine or feces to the environment, which continues the transmission of schistosomiasis [1]. Eggs are deposited in tissues and organs of the host, such as the liver, and much of the disease pathology is a product of the immune response against these trapped ova, where the ensuing granulomatous lesions lead to fibrosis, which can cause severe circulatory impairment of the affected organs [2]. Despite decades of concentrated research, there is still no effective and practical vaccine against the disease [3]. Mass chemotherapy using praziquantel (PZQ)—the only effective
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