Nanopartículas de quitosana como novo sistema de liberação vacinal contra a esquistossomose

Abstract

Schistosomiasis remains one of the worlds most prevalent diseases and until now there isnt an effective vaccine against the Schistosoma mansoni infection. Although oral vaccination has numerous advantages over parenteral injection, degradation of the vaccine in the gastrointestinal and low uptake in the gut-associated lymphoid tissue limit the development of oral vaccines. Association of the vaccine with carrier systems based on micro and nanoparticles may prevent its degradation, stimulate the M-cells to transport the vaccine to the dome of the Peyers Patches and also promote the activation of immune system. Chitosan has been shown a suitable vaccine carrier because of its biocompatibility, biodegradability and its ability to easily form nanoparticles, when associated with protein and also with nucleic acids. To ensure the stability in the gastrointestinal tract of the nanoparticles that have the antigen adsorbed on its surface, a coating process with sodium alginate has been done with promising results. In this context, the aim of this study was to prepare and characterize nanoparticles associated with the protein Rho1-GTPase of S. mansoni (SmRho) and to the pDNA-Rho encoding the protein Rho1-GTPase, with the first one being coated with sodium alginate, and evaluate the protective immunity induced by these candidates of vaccine. The characterization of the nanoparticles showed that they had a size and zeta potential suitable for their use as oral vaccine and also the suspensions of the particles showed a good stability when exposed to simulate gastric fluid (SGF) and simulated intestinal fluid (SIF). The various formulations prepared, with or without the addiction of the adjuvant CpG, were administered to mouse C57BL/6, either orally or intramuscularly. The group that had the higher levels of antibody, as measured by ELISA, was the group immunized with alginate coated chitosan nanoparticles associated with SmRho administered by intramuscular route. However, this group showed no significant protection after the cercariae infection. Among the groups immunized by oral route, the one that was administered with alginate coated chitosan nanoparticles loaded with SmRho and chitosan-DNA particles, showed the best results in general. This group had considerable amounts of antibodies and also had the highest percentage of protection, with a decrease of 57% of the worms recovered. In conclusion, although the formulations administered orally has not produced high levels of antibodies, most had a good protective profile, showing the vast potential yet to be explored in the use of nanoparticles as vaccine carrier systems.