Evaluation of the immunogenic potential of recombinant Mycobacterium bovis BCG expressing the ASP-2 and TC24 proteins from Trypanosoma cruzi

Abstract

Although drugs have been employed over the past years to treat Chagas disease, they 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. Consequently, to deal with this disease, prophylaxis seems to be a better strategy, with recombinant subunit vaccines showing promising results. Among those, 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 expressing a fraction of the amastigote surface protein 2 (ASP-2) and the 24 kDa flagellar calcium-binding protein (TC24) of T. cruzi. To accomplish this, four groups of BALB/c female mice (n = 10) were vaccinated with 0.9% saline solution (Group 1), non-transformed BCG Pasteur (Group 2), rBCG/pUS977/ASP-2 (Group 3) or rBCG/pUS977/TC24 (Group 4). Cellular responses, assessed by cytokine expression from cultured and protein stimulated splenocytes, were statistically higher for both vaccinal formulations when compared with basal levels (Group 1) and non-transformed BCG (Group 2). Group 3 achieved better results for interleukins 10 and 17, while interferon γ was greatly stimulated by vaccination with Group 4. 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.