Tc52 or its N-terminal domain DNA carried by attenuated Salmonella as a DNA delivery system, are able to confer protection against Trypanosoma cruzi infection

MATOS MN, CAZORLA SI, SANCHEZ ALBERTI A, MALCHIODI EL

Congreso; First French - Argentine Immunology Congress.LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010

Tc52 is a T. cruzi protein with glutation transferase activity, which has immunomodulatory properties. Analyzing candidates for a vaccine against Chagas´ disease we have studied the ability of the DNAs codifying for Tc52 and its amino and carboxi-terminal domains (N-term and C-term) to confer protection against T. cruzi infeccion. As a DNA delivery system we used atenuated Salmonella enterica serovar Typhimurium aro A 7207 (S). Four groups of C3H mice were immunized twice with: GI: S (Salmonella carrying an empty pcDNA3.1, as control group), GII: STc52 (S with pcDNA3.1-Tc52), GIII: SN-term (S with pcDNA3.1-N-term), GIV: SC-term (S with pcDNA3.1-C-term). Eighteen days after the last immunization, delayed-type hypersensitivity (DTH) test was performed. Two days later, mice were infected with 1000 bloodstream trypomastigotes (RA strain). Parasitemia was monitored by counting peripheral blood parasites every 2 days. Weight lose was monitored as a measure of physical health. After immunization all test groups developed a cellular immune response specific against the recombinants proteins (p<0.001). The GII: STc52 reacted against the two domains (p<0.05 for N-term and p<0.001 for C-term). GIII and GIV reacted against the whole protein (p<0.01 and p<0.05 for GIII and GIV, respectively). The area under the curve of parasitemia vs. time pi, for GIV, GII and GIII was respectively, 3.0, 7.0 and 7.2 times lower than the control. At 25 days pi all the test groups showed lower weight lose comparing with control, the difference was more important in the case of GII and GIII (p<0.05). We can conclude that the 3 vaccine candidates generated protection against T. cruzi infection. However, the N-terminal domain produces a similar protection than the whole Tc52 but a higher protection than the C-terminal domain, which suggest N-term domain of Tc52 would be an excellent candidate for the development of a vaccine against T. Cruzi.