| Summary: | Schistosomiasis is a neglected tropical disease caused by parasitic blood flukes of the genus <i>Schistosoma</i>, 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 <i>Schistosoma mansoni</i> 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 <i>in vitro</i> with anti-schistosome cholinesterase (<i>Sm</i>ChE) IgG, both schistosomula and adult worms displayed significantly decreased ChE activity, which eventually resulted in parasite death. Vaccination with individual <i>Sm</i>ChEs, or a combination of all three <i>Sm</i>ChEs, 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 <i>Sm</i>AChE1 in trial 1. Egg viability, as determined by egg hatching from liver homogenates, was significantly reduced in the groups vaccinated with the <i>Sm</i>ChE cocktail (40%) and <i>Sm</i>AChE2 (46%). Furthermore, surviving worms from each vaccinated group were significantly stunted and depleted of glycogen stores, compared to controls. These results suggest that <i>Sm</i>ChEs could be incorporated into a vaccine against schistosomiasis to reduce the pathology and transmission of this debilitating disease.
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