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 microg 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 IFNgamma-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 IFNgamma production, would be good candidates for effective therapeutic vaccination against T. cruzi infection.
Zapata-Estrella
Hiatzy
H
Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico.
Hummel-Newell
Caroline
C
Sanchez-Burgos
Gilma
G
Escobedo-Ortegon
Javier
J
Ramirez-Sierra
Maria Jesus
MJ
Arjona-Torres
Arletty
A
Dumonteil
Eric
E
D000208:Acute Disease; D000818:Animals; D014355:Chagas Disease / Q000276:immunology / Q000628:therapy*; D002908:Chronic Disease; D051379:Mice; D008813:Mice, Inbred ICR; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
D019444:Vaccines, DNA