Schistosoma mansoni Stomatin Like Protein-2 Is Located in the Tegument and Induces Partial Protection against Challenge Infection

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.

Immunization with rP22 induces protective immunity against Schistosoma mansoni: Effects on granuloma down-modulation and cytokine production

“…The 96-well plates (Nunc, Denmark) were maintained in an incubator at 37 • C with 5% CO 2 . For cytokine assays polymyxin B (30 g/ml) was added to the cultures and this treatment completely abrogate the cytokine response to LPS as previously described [26]. Culture supernatants were collected after 24 h of rP22 or SWAP stimulation for TNF-␣ analysis and after 72 h for IL-10, IL-4, TGF-␤ and IFN-␥ analysis.…”

Murine schistosomiasis as a model for human schistosomiasis mansoni: similarities and discrepancies

“…They reported that such an immune evasion mechanism may have profound implications for vaccination against schistosomes. More recently, based upon murine studies, Farias et al (2010) showed that S. mansoni stomatin-like protein 2 (SmStoLP-2) had protective potential against schistosomiasis and could be useful in a combination vaccine.…”

CpG oligodeoxynucleotide ligand potentiates the activity of the pVAX1-Sj26GST

“…However, the combination with CpG enhanced the production of IFN-γ and TNF-α, although it also increased the secretion of IL-4 and IL-10 in rats vaccinated by pVAX1-Sj26GST plus CpG, which, however, remained lower compared to that in pVAX1-vaccinated rats. The elevated IFN-γ and TNF-α levels in response to the combination with CpG may be associated with the enhancement of protection conferred by pVAX1-Sj26GST vaccination since the protection induced by several schistosoma vaccines was associated with elevated production of IFN-γ and TNF-α (19,20). Our data also suggested that triggering more than one TLR may be an effective approach to optimize immune responses to vaccination.…”