Abstract
BackgroundSchistosomiasis affects more than 200 million individuals worldwide, with a further 650 million living at risk of infection, constituting a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection, and the development of an effective vaccine still remains the most desirable means of control for this disease.Methodology/Principal FindingsHerein, we report the cloning and characterization of a S. mansoni Stomatin-like protein 2 (SmStoLP-2). In silico analysis predicts three putative sites for palmitoylation (Cys11, Cys61 and Cys330), which could contribute to protein membrane association; and a putative mitochondrial targeting sequence, similar to that described for human Stomatin-like protein 2 (HuSLP-2). The protein was detected by Western blot with comparable levels in all stages across the parasite life cycle. Fractionation by differential centrifugation of schistosome tegument suggested that SmStoLP-2 displays a dual targeting to the tegument membranes and mitochondria; additionally, immunolocalization experiments confirm its localization in the tegument of the adult worms and, more importantly, in 7-day-old schistosomula. Analysis of the antibody isotype profile to rSmStoLP-2 in the sera of patients living in endemic areas for schistosomiasis revealed that IgG1, IgG2, IgG3 and IgA antibodies were predominant in sera of individuals resistant to reinfection as compared to those susceptible. Next, immunization of mice with rSmStoLP-2 engendered a 30%–32% reduction in adult worm burden. Protective immunity in mice was associated with specific anti-rSmStoLP-2 IgG1 and IgG2a antibodies and elevated production of IFN-γ and TNF-α, while no IL-4 production was detected, suggesting a Th1-predominant immune response.Conclusions/SignificanceData presented here demonstrate that SmStoLP-2 is a novel tegument protein located in the host-parasite interface. It is recognized by different subclasses of antibodies in patients resistant and susceptible to reinfection and, based on the data from murine studies, shows protective potential against schistosomiasis. These results indicate that SmStoLP-2 could be useful in a combination vaccine.
Highlights
Schistosomiasis is an important parasitic disease, caused by trematode worms of the genus Schistosoma; it affects approximately 200 million of individuals primarily in developing countries and an estimated additional 500 to 600 million are at risk
We present the characterization of one of these molecules, a stomatin like protein 2 (SmStoLP-2)
Sequence analysis predicts signals that could contribute to protein membrane association and mitochondrial targeting, which was confirmed by differential extractions of schistosome tegument membranes and mitochondria
Summary
Schistosomiasis is an important parasitic disease, caused by trematode worms of the genus Schistosoma; it affects approximately 200 million of individuals primarily in developing countries and an estimated additional 500 to 600 million are at risk. Until October 2003, schistosome research suffered from limited genomic information; this situation has changed significantly with the simultaneous publication of the S. mansoni and S. japonicum transcriptomes [7,8]. These initiatives, together with the advent of entire S. mansoni genome sequencing, all boosted by advances in bioinformatics, have markedly changed the schistosome vaccine research field. Even though an effective treatment exists, it does not prevent re-infection, and the development of an effective vaccine still remains the most desirable means of control for this disease
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