Avaliação de epítopos derivados de micronema mic8 e de antígeno de superfície srs52a de toxoplasma gondii, associados a diferentes adjuvantes, como possíveis antígenos vacinais contra a toxoplasmose

Abstract

Toxoplasmosis, a zoonosis caused by the mandatory intracellular protozoan Toxoplasma gondii, is a disease virtually capable of infecting any homeothermic host, with cases recorded in several species of birds and mammals, including humans. This disease is relevant not only for humans, since infection with this protozoan is associated with substantial financial losses in livestock, especially in sheep and goats. Infected humans can be asymptomatic or have several different symptoms, the most serious of which are usually seen in individuals who belong to the groups at risk for this disease, such as immunocompromised patients or pregnant women whose concepts can be infected. In the hypothesis of vertical transmission from the pregnant woman to the fetus, toxoplasmosis can cause several symptoms, which can be less severe, such as cases of mild chorioretinitis, even the most severe manifestations, characterized by malformations of the central nervous system from fetus and even intrauterine death and abortion. For immunocompromised individuals, toxoplasmosis also constitutes significant risks, since latent parasitic cysts in the central nervous system can reactivate the inflammatory process, causing neurotoxoplasmosis, which can be fatal. Although it is capable of causing great damage to the host, possibly leading to death or causing sequelae that impair the quality of life of the affected person for the rest of his life, this disease continues to be neglected. As a result of the lack of vigilance and awareness about this disease, both by health professionals and the population in general, several outbreaks occur annually in our country and around the world, always being characterized by the delay in reaching the correct diagnosis. In the present work, we studied an alternative that can mitigate the effects of this disease through the principle of immunoprophylaxis. To achieve this goal, three peptides were predicted containing 15 amino acid residues each, using available prediction tools with the potential to act as epitopes for B cells. The regions were analyzed looking for the two most immunodominant sequences of the secreted protein 8 by the Micronema organelle (MIC8) and one of the sequences related to 52A surface antigens (SRS52A). The synthesized peptides were added immunoadjuvant compounds, such as aluminum hydroxide, or lectin derived from Synadenium carinatum (ScLL), or propranolol, which were used to immunize mice. Tests were carried out to quantify the levels of antibodies and cytokines produced, in addition to the parameters of survival and parasitic load after 30 days of infection. It was observed that all animals immunized with peptides produced specific antibodies to the original protein, except for groups immunized with propranolol. Regarding the analysis of produced cytokines, the groups immunized with ScLL had lower concentrations of cytokines than the non-immunized group, however the ratio of cytokines of the Th1 profile to Th2 was higher. In addition, the animals immunized with peptides and ScLL survived longer than those not immunized, although the difference was not statistically significant. Finally, the parasitic load, when the ScLL group was present, was significantly lower, being around 25% of the load observed in the non-immunized animals. In summary, the results obtained demonstrate that the predicted peptides retained their immunodominant characteristics and, together with ScLL, were able to induce a more effective response against infection, particularly in relation to the chronic phase, thus presenting itself as a potential tool in future prevention studies in the epidemiological chain of toxoplasmosis.