Characterization of a Partially Protective B-cell Epitope within the 62 kDa Antigen of <italic>Schistosoma japonicum</italic>

Abstract

Approximately 200 million people worldwide currently suffer from schistosomiasis, one of the most important human parasitic diseases. Although an established infection can be treated with anthelminthics and praziquantel, vaccination would be the ideal method for integral control of schistosomiasis. Schistosoma mansoni IrV-5, recommended as a vaccine candidate by the World Health Organization/Special Programme for Research and Training in Tropical Diseases, produced high protection in animal models. We therefore focused on its homolog, the Schistosoma japonicum 62 kDa antigen, and analyzed it using B cell/antibody-related databases and analysis tools for the prediction of B-cell epitopes. Epitope B3 was selected for further investigation. Experiments using a murine model indicated that mice immunized with B3 resulted in lymphocytes proliferation and produced high levels of specific immunoglobulin G and G1, but did not produce impressive cytokines. The vaccination showed partial protective immunity, measured by worm burden and anti-fecundity immunity against S. japonicum. These results indicated that the epitope B3 from S. japonicum 62-kDa antigen might act as a candidate immunogen for future epitope vaccine investigation.

The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

“…Consistent with results described previously by our group [13,14], T3- and B3-PDDV vaccinations induced significant reductions in worm and egg burdens in this experiment. Vaccination with T3-PDDV resulted in a 35.80% worm burden reduction and a 51.60% egg (liver) reduction compared to 18K-PDDV-vaccinated controls.…”

“…The DNA sequences used to encode the respective S. japonicum epitopes were designed based on the published S. japonicum DNA sequences for Sj22.6 [13], Sj62 [14] and Sj97 [15]. …”

“…These vaccination modalities have been tested in animal models and some formulations have proved successful [37,38], suggesting that multicomponent formulations can be used to develop effective anti-schistosome vaccines. Recently, we demonstrated that vaccination with PDDV based on a T cell-epitope (P5, in this study named T3) derived from the Sj22.6 tegument antigen or a B cell-epitope (B3) derived from the Sj62 myosin sequence all induced partial protection against S. japonicum challenge in mice [13,14]. In this study we predicted and selected six additional peptide epitopes derived from full-length Sj22.6, Sj62, and Sj97 antigens shown to have the potential of eliciting protective immunity in various other studies [6,13,14,39-42].…”

“…Recently, we demonstrated that vaccination with PDDV based on a T cell-epitope (P5, in this study named T3) derived from the Sj22.6 tegument antigen or a B cell-epitope (B3) derived from the Sj62 myosin sequence all induced partial protection against S. japonicum challenge in mice [13,14]. In this study we predicted and selected six additional peptide epitopes derived from full-length Sj22.6, Sj62, and Sj97 antigens shown to have the potential of eliciting protective immunity in various other studies [6,13,14,39-42]. The experiments were aimed at improving the immunoreactivity and protective efficacy of the peptide-based approach by comparing immune responses following vaccinations with either single or multicomponent formulations in mice subsequently infected with S. japonicum .…”

“…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. Although 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]. Epitope-based vaccines offer the prospect of targeted immunity resulting in safer and more effective antigen-specific immune responses [18].…”