Therapeutic administration of DNA vaccines to control an ongoing infection with T. cruzi may represent an additional Eric Dumonteil 7 alternative for Chagas disease control. The concept was demonstrated in mice acutely or chronically infected, and in both cases the administration of only two doses of DNA vaccine encoding TSA-1 or Tc24 antigens was sufficient to limit disease progression, as treated mice presented increased survival and reduced cardiac tissue damage, as assessed by histopathologic analysis [104] . A comparative study of different DNA vaccines identified Tc52 antigen as another therapeutic vaccine candidate, while DNA vaccines encoding antigens from the TS family previously found to be protective had no signifiacnt therapeutic effect [105] . It was found that therapeutic vaccination rapidly induced spleen cell proliferation, including IFNγ-producing CD4 + and CD8 + T cells, while the effects on cardiac tissue inflammation and parasite burden take longer to be detectable [106] . Importantly, in all these studies, therapeutic vaccination of T. cruzi infected mice did not result in an increased inflammatory reaction in the heart, confirming that it is safe to stimulate the immune response of T. cruzi infected mice and that attacking the parasite can lead to a reduction of pathology. These studies thus open very attractive perspectives for the control of T. cruzi infection, and further studies on the efficacy of DNA vaccines encoding other antigens and on the immune mechanisms underlying their therapeutic effect should provide clues for the optimization of this strategy.