Evaluation of prime-boost vaccination strategies against Schistosoma mansoni experimental infection applying DNA vaccines.

Schistosomiasis is one of the most important diseases due to helminthes, affecting approximately 207 million people worldwide. The treatment is based on Praziquantel and Oxamniquine drugs, however these drugs do not avoid reinfections and are inefficient against worm immature stages. Therefore, the development of an efficient vaccination strategy is an essential component in the control of this disease. The aim of this work was to study the immune response induced by immunization with DNA-Sm14 vaccine in combination with DNA-Hsp65 using prime-boost protocols, which were heterologous or homologous. The heterologous prime-boost vaccination did not modify IgG2a production, but decreased IFN- and IL-10 production compared to animals that received only DNA-Sm14. After infection, this prime-boost strategy was not effective in reducing the worm burden of animals, while vaccination with DNA-Sm14 induced partial reduction. Using both vaccines in the homologous prime-boost model, we found that the modification of the strategy did not alter IgG2a production, although reduced IFN- production by cells recovered from the broncho-alveolar space compared to DNA-Sm14 immunized mice. After infection, immunization with DNA-Sm14/DNA-Hsp65 didnt modify the animals parasitic burden, however systemically, reduced eosinophils number. When the profile of memory cells in vaccinated animals was evaluated, we verified increased numbers of CD8+ T cells and lower numbers of CD4+ T cells in the spleen of animals immunized with both vaccines simultaneously. In conclusion, the vaccines DNA-Sm14 and DNA-Hsp65 in both strategies, prime-boost heterologous or homologous, were not able to generate protection against experimental infection with S. mansoni, and we propose that, partly, the decrease of IFN-, IL-10 levels, increase of IgG1/IgG2a ratio and the stimulation of CD8+ T cells rather than CD4+, may have contributed to the low efficacy of the vaccination protocols tested. (AU)