Abstract
BackgroundSchistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV) (T3-PDDV and B3-PDDV, respectively) capable of eliciting immune responses against the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6) and a 62 kDa fragment of myosin (Sj62), respectively.ResultsIn this study, we developed PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential in vivo. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components) formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations.ConclusionsOur data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.
Highlights
Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species
The S. japonicum Sj22.6 [13], Sj62 [14], and Sj97 [15] antigens, which are all important components of schistosome adult worm antigens (SWA), have been shown to be promising vaccine candidates, other approaches have focused on eliciting specific B-cell and Th-cell responses by identifying different antigenic determinants in potential vaccine targets [16,17]
These results indicate that C2- and C3-peptide-DNA dual vaccines (PDDV) vaccination induced cytotoxic responses associated with IFN-g production and IgG and IgG2a production
Summary
Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. We developed partially protective, single Th- and B cellepitope-based peptide-DNA dual vaccines (PDDV) (T3-PDDV and B3-PDDV, respectively) capable of eliciting immune responses against the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6) and a 62 kDa fragment of myosin (Sj62), respectively. Schistosomiasis is one of the most important neglected tropical diseases (NTDs) and remains a major public health problem in endemic countries [1,2]. The major challenge in the development of anti-schistosome vaccines is to use defined antigens to stimulate the appropriate immune response that lead to protection. Epitope-based vaccines offer the prospect of targeted immunity resulting in safer and more effective antigen-specific immune responses [18]. The levels of protection induced by both vaccines were limited
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