Abstract
Current schistosomiasis control strategies are mainly based on chemotherapy, but the development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. When it comes to vaccine candidates, several genes encoding Schistosoma mansoni proteins expressed at the mammalian host–parasite interface have been tested. Among the most promising molecules are the proteins present on the tegument and digestive tract of the parasite. In this study, we evaluate the potential of SmKI-1, the first Kunitz-type protease inhibitor functionally characterized in S. mansoni, as a vaccine candidate. Bioinformatic analysis points to the C-terminal fragment as the main region of the molecule responsible for the development of a potential protective immune response induced by SmKI-1. Therefore, for the vaccine formulations, we produced the recombinant (r) SmKI-1 and two different fragments, its Kunitz (KI) domain and its C-terminal tail. First, we demonstrate that mice immunized with recombinant SmKI-1 (rSmKI-1) or its fragments, formulated with Freund’s adjuvant, induced the production of IgG-specific antibodies. Further, all vaccine formulations tested here also induced a Th1-type of immune response, as suggested by the production of IFN-γ and TNF-α by protein-stimulated cultured splenocytes. However, the protective effect conferred by vaccination was only observed in groups which received rSmKI-1 or C-terminal domain vaccines. Mice administered with rSmKI-1 demonstrated reduction of 47% in worm burden, 36% in egg number in mouse livers, and 33% in area of liver granulomas. Additionally, mice injected with C-terminal domain showed reduction of 28% in worm burden, 38% in egg number in liver, and 25% in area of liver granulomas. In contrast, KI domain immunization was unable to reduce worm burden and ameliorate liver pathology after challenge infection. Taken together, our data demonstrated that SmKI-1 is a potential candidate for use in a vaccine to control schistosomiasis, and its C-terminal tail seems to be the main region of the molecule responsible for protection conferred by this antigen.
Highlights
Schistosomiasis is a disease caused by trematode worms of the genus Schistosoma that affects about 207 million people in 76 countries worldwide [1, 2]
Considering that SmKI-1 plays a vital role in parasite survival, we decided to evaluate its potential as vaccine candidate against schistosomiasis
Immunolocalization experiments using polyclonal antirSmKI-1 indicated that SmKI-1 is mainly present in the intestinal tract in larval stage schistosomula, it has previously reported to be localized on the tegument in adult worms [9]
Summary
Schistosomiasis is a disease caused by trematode worms of the genus Schistosoma that affects about 207 million people in 76 countries worldwide [1, 2]. The treatment, effective, is facing some limitations because the chemotherapy is active only against adult forms of the parasite (not acting on the larval form) and mass treatment does not prevent reinfection [3,4,5]. The lack of new therapeutic drugs and preventive measures, as well as the high disease burden caused by the reinfection are justifications for developing a vaccine against schistosomiasis [4]. Many efforts have been accomplished for the development of an effective vaccine against schistosomiasis [4, 6]. Most of the important vaccine targets described up to date are proteins located at the parasite/host interface, since they are commonly associated with mechanisms of escape from the host immune system or other adaptation to parasitism [7] and the two major interfaces are the outer tegument and the gastrodermis [6, 8]
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