The development of a vaccine against schistosomiasis and also the availability of a more sensitive diagnosis test are important tools to help chemotherapy in controlling disease transmission. Bioinformatics tools, together with the access to parasite genome, published recently, should help generate new knowledge on parasite biology and search for new vaccines or therapeutic targets and antigens to be used in the disease diagnosis. Parasite surface proteins, especially those expressed in schistosomula tegument, represent interesting targets to be used in vaccine formulations and in the diagnosis of early infections, since the tegument represents the interface between host and parasite and its molecules are responsible for essential functions to parasite survival. In this paper we will present the advances in the development of vaccines and diagnosis tests achieved with the use of the information from schistosome genome focused on parasite tegument as a source for antigens.

The successful development of vaccines depends on the knowledge of the immunological mechanisms associated with the elimination of the pathogen. In the case of schistosomes, its complex life cycle and the mechanisms developed to evade host immune system, turns the development of a vaccine against the disease into a very difficult task. Identifying the immunological effector mechanisms involved in parasite attrition and the major targets for its response is a key step to formulate an effective vaccine. Recent studies have described some promising antigens to compose a subunit vaccine and have pointed to some immune factors that play a role in parasite elimination. Here, we review the immune components and effector mechanisms associated with the protective immunity induced by those vaccine candidates and the lessons we have learned from the studies of the acquired resistance to infection in humans. We will also discuss the immune factors that correlate with protection and therefore could help to evaluate those vaccine formulations in clinical trials.

BackgroundA vaccine against schistosomiasis would have a great impact in disease elimination. Sm29 and Sm22.6 are two parasite tegument proteins which represent promising antigens to compose a vaccine. These antigens have been associated with resistance to infection and reinfection in individuals living in endemic area for the disease and induced partial protection when evaluated in immunization trials using naïve mice.Methodology/principals findingsIn this study we evaluated rSm29 and rSm22.6 ability to induce protection in Balb/c mice that had been previously infected with S. mansoni and further treated with Praziquantel. Our results demonstrate that three doses of the vaccine containing rSm29 were necessary to elicit significant protection (26%–48%). Immunization of mice with rSm29 induced a significant production of IL-2, IFN-γ, IL-17, IL-4; significant production of specific antibodies; increased percentage of CD4+ central memory cells in comparison with infected and treated saline group and increased percentage of CD4+ effector memory cells in comparison with naïve Balb/c mice immunized with rSm29. On the other hand, although immunization with Sm22.6 induced a robust immune response, it failed to induce protection.Conclusion/significanceOur results demonstrate that rSm29 retains its ability to induce protection in previously infected animals, reinforcing its potential as a vaccine candidate.

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Sm16 is an immunomodulatory protein that seems to play a key role in the suppression of the cutaneous inflammatory response during Schistosoma mansoni penetration of the skin of definitive hosts. Therefore, Sm16 represents a potential target for protective immune responses induced by vaccination. In this work, we generated the recombinant protein rSm16 and produced polyclonal antibodies against this protein to evaluate its expression during different parasite life-cycle stages and its location on the surface of the parasite. In addition, we analyzed the immune responses elicited by immunization with rSm16 using two different vaccine formulations, as well as its ability to induce protection in Balb/c mice. In order to explore the biological function of Sm16 during the course of experimental infection, RNA interference was also employed. Our results demonstrated that Sm16 is expressed in cercaria and schistosomula and is located in the schistosomula surface. Despite humoral and cellular immune responses triggered by vaccination using rSm16 associated with either Freund's or alum adjuvants, immunized mice presented no reduction in either parasite burden or parasite egg laying. Knockdown of Sm16 gene expression in schistosomula resulted in decreased parasite size in vitro but had no effect on parasite survival or egg production in vivo. Thus, our findings demonstrate that although the vaccine formulations used in this study succeeded in activating immune responses, these failed to promote parasite elimination. Finally, we have shown that Sm16 is not vital for parasite survival in the definitive host and hence may not represent a suitable target for vaccine development.

BackgroundPrevious studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host.Methodology and Principal FindingsThe aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs.ConclusionTaken together, these findings demonstrate that S. mansoni schistosomula tegument can modulates experimental airway inflammation.

Schistosome-host interaction is influenced by multiple factors, such as the type of immune response developed by the host, host genetic background, intensity, and number of infections. Those factors not only affect the development and elimination of Schistosoma mansoni , but also the pathology triggered by infection with this parasite. In the present study, we assessed the parasitological, pathological, and immunological aspects elicited by infection and reinfection in 2 different mouse strains commonly used as models in studies on schistosomiasis: BALB/c and C57BL/6. No differences in worm burden recovery or in the number of eggs per gram of intestine or feces were observed between the strains or between infected and reinfected mice from the same strain. However, the number of eggs trapped in the liver of the reinfected mice was significantly higher than the number of eggs in the liver of the infected animals. But, the granulomatous area was significantly lower in reinfected animals than in infected ones. Additionally, granuloma in the infected BALB/c mice was greater than in infected C57BL/6 animals. Regarding the cytokine profile, spleen cells from the infected/reinfected C57BL/6 mice produced higher interleukin 10 (IL-10) levels against egg antigens than BALB/c-infected/reinfected mice. BALB/c mice, in contrast, produced significantly higher IL-4 and IL-13 cytokines after infection/reinfection than the C57BL/6 mice, with the highest levels of IL-13 being observed after reinfection. Our results demonstrate that, although different host backgrounds did not impact resistance to S. mansoni , they result in different immunological profiles that suggest different pathological impacts on the liver.

In schistosomiasis, the current control strategy does not prevent reinfection, therefore, vaccine strategies are essential to combat the Schistosoma mansoni. The efficacy vaccine depends on parasite stage and effective adjuvant. We have recently demonstrated that S. mansoni schistosomula tegument (Smteg) is able to activate dendritic cells up regulate CD40 and CD86 molecules and induce a partial protection in mice (43-48%) when formulated with Freund's adjuvant. In this study we evaluated the ability of Smteg + alum or Smteg + alum + CpG-ODN to induce protection in mice. Our results demonstrate that Smteg + alum + CpG-ODN induced a partial reduction in worm burden (43.1%), reduction in the number of eggs eliminated in the feces. The protective response was associated with a predominant Th1 type of immune response, with increased production of specific IgG2c, IFN-γ and TNF-α, B cells proliferation and CD4 cells and macrophages activation.