Control of Trypanosoma cruzi infection and changes in T-cell populations induced by a therapeutic DNA vaccine in mice

Previous work showed that immunotherapy with a DNA vaccine encoding Trypanosoma cruzi antigen TSA-1 reduced cardiac tissue damage and improved survival in mice when administered during the acute or chronic phases of T cruzi infection. In the present study, we investigated changes in T-cell populations induced by DNA vaccine immunotherapy. ICR mice were infected with 500 T cruzi blood trypomastigotes and treated during the acute or chronic phases with two 100 mu g doses of DNA vaccine. Analysis of stained splenocytes by flow cytometry indicated that the therapeutic vaccine induced a rapid increase in the number of CD4(+) and CD8(+) T cells in both the acute and chronic phases. Also, there was a rapid increase in T cruzi-specific IFN gamma-producing CD8(+) T cells following treatment during the chronic phase. The effects of these changes on the control of infection required longer time periods to be detectable but resulted in a reduction in myocarditis and T cruzi parasite burden in both phases of the infection, as assessed by histopathologic analysis and semi-quantitative PCR detection of T cruzi in cardiac tissue. These results suggest that DNA vaccines that induce CD8(+) T-cells activity and IFN gamma production, would be good candidates for effective therapeutic vaccination against T cruzi infection. (C) 2005 Elsevier B.V. All rights reserved.