Effect of a combination DNA vaccine for the prevention and therapy of Trypanosoma cruzi infection in mice Role of CD4+ and CD8+ T cells

Chagas disease is a major public health problem with about 10 million infected people and DNA vaccines are a promising alternative for the control of Trypanosoma cruzi the causing agent of the disease We tested here a new DNA vaccine encoding a combination of two leading parasite antigens TSA-1 and Tc24 for the prevention and therapy of T cruzi infection Immunized Balb/c mice challenged by T cruzi presented a significantly lower parasitemia and inflammatory cell density in the heart compared to control mice Similarly the therapeutic administration of the DNA vaccine was able to significantly reduce the parasitemia and inflammatory reaction in acutely infected Balb/c and C57BL/6 mice and reduced cardiac tissue inflammation in chronically infected ICR mice Therapeutic vaccination Induced a marked increase in parasite-specific IFN gamma producing CD4(+) and CD8(+) T cells in the spleen as well as an increase in CD4(+) and CD8(+) T cells in the Infected cardiac tissue In addition some effect of the DNA vaccine could still be observed in CD4-knockout C57BL/6 mice which presented a lower parasitemia and Inflammatory cell density but not in CD8-deficient mice in which the vaccine had no effect These results indicate that the activation of CD8(+) T cells plays a major role in the control of the infection by the therapeutic DNA vaccine and to a somewhat lesser extent CD4(+) T cells This observation opens interesting perspectives for the potentiation of this DNA vaccine candidate by including additional CD8+ T cell antigens/epitopes in future vaccine formulations (C) 2010 Elsevier Ltd All rights reserved