Therapeutical effects of vaccine from Trypanosoma cruzi amastigote surface protein 2 by simultaneous inoculation with live parasites

The aim of this study was to evaluate the efficacy of vaccine using replication‐deficient human recombinant Type 5 replication‐defective adenoviruses (AdHu5) carrying sequences of the amastigote surface protein 2 (ASP2) (AdASP2) in mice infected with the Trypanosoma cruzi ( T cruzi) Y strain. A total of 16 A/Sn mice female were distributed into four groups, as follows (n = 4 per group): Group 1 – Control Group (CTRL); Group 2 – Infected Group (TC): animals were infected by subcutaneous route with 150 bloodstream trypomastigotes of T cruzi Y strain; Group 3 – Immunized Group (AdASP‐2): animals were immunized by intramuscular injection (im) route with 50 µL of AdSP‐2 (2 × 10 8 plaque forming units [pfu]/cam) at day 0; Group 4‐Immunized and Infected Group (AdASP‐2+TC): animals were immunized by im route with 50 µL of ASP‐2 (2 × 10 8 pfu/cam) and infected by T cruzi at the same day (day 0). It was observed a significant decrease of nests in the group that was immunized with AdASP‐2 and infected on the same day. Tumor necrosis factor alpha (TNF‐α) and inducible nitric oxide synthase (iNOS) gene expressions showed a significant increase in the AdASP‐2+TC group when compared to TC group, but it was noted that Cyclooxygenase‐2 (Cox‐2) was increased in TC group when compared to AdASP‐2+TC group. Increase of matrix metalloproteinases‐2 (MMP‐2) and decrease of MMP‐9 immunoexpression in the AdASP‐2+TC group was noticed as well. Oxidative DNA damage was present in myocardium for AdASP‐2+TC group as a result of 8‐hydroxydeoxyguanosine immunoexpression. Taken together, our results highlighted an increased oxidative stress, MMP‐2 activity and inflammatory host response promoted by AdASP‐2 against T cruzi infection. Our results highlighted the increase oxidative stress, matrix metalloproteinases‐2 (MMP‐2) activity and inflammatory host response as mechanisms which play pivotal role to protection elicited with AdASP‐2 against Trypanosoma cruzi infection.