Schistosomiasis is an important parasitic disease for which there is no available vaccine. We have focused on a functionally important antigen of Schistosoma mansoni, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective potential and antifecundity effect observed in murine models; and for its pivotal role in the immune evasion process. In the present study we report that a Sm-p80-based DNA vaccine formulation confers 38% reduction in worm burden in a nonhuman primate model, the baboon (Papio anubis). Animals immunized with Sm-p80-pcDNA3 exhibited a decrease in egg production by 32%. Sm-p80 DNA elicited specific immune responses that include IgG; its subtypes IgG1 and IgG2; and IgM in vaccinated animals. Peripheral blood mononuclear cells (PMBCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot forming units for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. Overall it appears that even though a mixed (Th1/Th2) type of humoral antibody response was generated following immunization with Sm-p80; the dominant protective immune response is Th1 type. These data reinforce the potential of Sm-p80 as an excellent vaccine candidate for schistosomiasis.
Advent of an effective schistosome vaccine would contribute significantly toward reducing the disease spectrum and transmission of schistosomiasis. We have targeted a functionally important antigen, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective and antifecundity potentials, and important role in the immune evasion process. In this study, we report that using two vaccination approaches (prime boost and recombinant protein), Sm-p80-based vaccine formulation(s) confer up to 70% reduction in worm burden in mice. Animals immunized with the vaccine exhibited a decrease in egg production by up to 75%. The vaccine elicited strong immune responses that included IgM, IgA, and IgG (IgG1, IgG2a, IgG2b, and IgG3) in vaccinated animals. Splenocytes proliferated in response to Sm-p80 produced Th1 and Th17 response enhancing cytokines. These results again emphasize the potential of Sm-p80 as a viable vaccine candidate for schistosomiasis.
SUMMARY
Although there is an effective drug (praziquantel) available for the treatment of schistosomiasis, yet the disease is still spreading unabated and is rampant in 76 countries. Control via praziquantel treatment has so far been insufficient in reducing the disease transmission. Therefore a vaccine in addition to other strategies, for example, improving sanitation and introduction of new drugs are essential to successfully control and eventually eradicate schistosomiasis. To this effect we have targeted a functionally important antigen, Sm-p80 as a vaccine candidate. In the present study, full length cDNA of Sm-p80 was cloned in VR1020, a FDA approved vector for human use. The protective efficacy of this vaccine formulation was tested in a murine model. Sm-p80-VR1020 vaccine formulation was able to induce 47% reduction in worm burden. Serology on samples obtained from vaccinated animals revealed a strong antibody response which included IgG and all of its subtypes, IgM and IgA. Proliferating splenocytes in response to recombinant Sm-p80 produced a wide spectrum of cytokines representing Th1, Th2 and Th17 types, as ascertained via RT-PCR analysis. These findings further strengthen the importance of Sm-p80 molecule as a vaccine candidate for intestinal schistosomiasis.
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