Avaliação da resposta imune induzida por Mycobacterium bovis BCG recombinante expressando antígenos de Trypanosoma cruzi contra doença de Chagas

Abstract

Chagas disease is a globally spread parasitic illness caused by the infection of the flagellated protozoan Trypanosoma cruzi. Although drugs, like benznidazole, have been employed over the past years, with some degree of efficacy, it is not without counter effects. Available drugs work mostly on the acute phase of infection, where diagnosis is hardly ever made, and present a plethora of negative side effects that ends in discontinuation of treatment by most patients. Consequently, prevention seems to be a better strategy to deal with this disease in particular. Among several prophylactic methods in development, Mycobaterium bovis Bacillus Calmette-Guérin (BCG) has recently been employed as vector for delivering T. cruzi antigens with positive results on immune response stimulus and protection against the infection. Following this perspective, this study aimed to characterize the immune response elicited by recombinant BCG (rBCG) expressing the calcium-binding 24 kDa protein (Tc24) and amastigote surface protein 2 (ASP-2) of T. cruzi. To accomplish this, five groups of BALB/c female mice (n = 10) were vaccinated with 0.9% saline solution (Group A), non-transformed BCG Pasteur (Group B), rBCG/pUS2000/asp-2 (Group C), rBCG/pUS977/asp-2 (Group D) or rBCG/pUS977/tc24 (Group E). Even though no significant humoral response was detected with any of the formulations through analysis with indirect ELISA of animal sera, cellular responses, assessed by cytokine expression from cultured and protein stimulated splenocytes, were statistically higher for all vaccinal formulations when compared with basal levels (Group A) and non-transformed BCG (Group B). Group D achieved better results for interferon γ and interleukin 10, while interleukins 4 and 17 where greatly stimulated by vaccination with Group C and Group E, with all formulations repressing interleukin 6. Even though further analyses are needed to evaluate the full efficacy of the constructions, the here presented results exhibit the potential of BCG vectored vaccines in eliciting Th1/Th2/Th17 mixed immune responses.