Schistosomiasis is a neglected tropical disease caused by several species of trematode of the genus Schistosoma. The disease affects more than 200 million people in the world and causes up to 280,000 deaths per year, besides having high morbidity due to chronic illness that damages internal organs. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Among the most promising molecules as vaccine candidates are the proteins present in the tegument and digestive tract of the parasite.
In this study, we describe for the first time Schistosoma mansoni syntenin (SmSynt) and we evaluate its potential as a recombinant vaccine. We demonstrate by real-time PCR that syntenin is mainly expressed in intravascular life stages (schistosomula and adult worms) of the parasite life cycle and, by confocal microscopy, we localize it in digestive epithelia in adult worms and schistosomula. Administration of siRNAs targeting SmSynt leads to the knock-down of syntenin gene and protein levels, but this has no demonstrable impact on parasite morphology or viability, suggesting that high SmSynt gene expression is not essential for the parasites in vitro. Mice immunization with rSmSynt, formulated with Freund's adjuvant, induces a Th1-type response, as suggested by the production of IFN-γ and TNF-α by rSmSynt-stimulated cultured splenocytes. The protective effect conferred by vaccination with rSmSynt was demonstrated by 30–37% reduction of worm burden, 38–43% reduction in the number, and 35–37% reduction in the area, of liver granulomas.
Our report is the first characterization of syntenin in Schistosoma mansoni and our data suggest that this protein is a potential candidate for the development of a multi-antigen vaccine to control schistosomiasis.
Schistosomiasis affects more than 200 million people worldwide and causes up to 280,000 deaths per year. In terms of global mortality and morbidity, this disease is the most important human helminth infection. Current control strategies are based on chemotherapy, but recurrent re-infection of people living in endemic areas makes many researchers, and also the World Health Organization, search for an effective vaccine to provide protection against schistosomiasis. Substantial efforts have been committed to the characterization of new antigens for an anti-schistosome vaccine and, in order to find new targets for vaccine and/or drug development, we searched transcriptomics and proteomics of Schistosoma mansoni and identified the protein syntenin (SmSynt) for analysis. In this study, we characterize SmSynt and evaluate its potential as a vaccine candidate to protect mice against S. mansoni infection. We demonstrate that SmSynt is expressed in schistosomula and adult worms, the intravascular stages of S. mansoni and it is located in the intestinal tract of the worms, an important host/parasite interface. Furthermore, vaccination of mice with rSmSynt confers partial protection against S. mansoni challenge infection and ameliorates parasite-induced liver pathology. Our data suggest that SmSynt is a potential candidate in the development of a vaccine against schistosomiasis.