Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental ChronicTrypanosoma cruziInfection in the Canine Model

Abstract

The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD). Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP) and an amastigote-specific glycoprotein (TcSSP4) were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.

Echocardiographic Findings in Canine Model of Chagas Disease Immunized with DNA Trypanosoma cruzi Genes

“…All infected/unimmunized dogs exhibited parasitemia starting on day 22 and lasting until day 55 postinfection, whereas the parasitemia of immunized/infected dogs occurred over a shorter time period, from day 32 to 46 postinfection [34] (Table 3). The effect of vaccination with these plasmids on macroscopic and microscopic damage caused by the chronic T. cruzi infection was to prevent splenomegaly and to avoid serious damage to the heart, in which lesions were limited to the subepicardial tissue [36] (Table 3). Table 3.…”

“…The rest of the positive control dogs (n = 6) were infected with an inoculum size that ranged from 50 × 10 3 to 2 × 10 6 metacyclic trypomastigotes. The amount of T. cruzi Ninoa strain inoculum had no effect on the severity of the canine ChD [34][35][36]38].…”

“…The aim of this study was to examine the usefulness of echocardiography in determining the prophylactic effect of the DNA vaccines on heart damage using T. cruzi genes cloned into an expression vector, which was intramuscularly injected to beagle dogs. To do so, we use this cardiac imaging method to measure hemodynamic parameters to determine whether echocardiography provides accurate data on the development of morphological changes in the heart of experimentally infected and immunized/infected chagasic dogs and if these data are consistent with those reported previously [34][35][36].…”

“…Immunological protection against experimental infection with T. cruzi has been studied since the second decade of the last century, testing many types of immunogens [31]. In our previous studies, TcSP (encoding trans-sialidase protein) and TcSSP4 (encoding amastigote-specific protein) genes were evaluated prophylactically as DNA vaccines in both murine and canine model of ChD [32][33][34][35][36]. The clinical, serological, and postmortem parameters obtained were consistent among these studies, showing a moderate effectiveness in protection against experimental ChD.…”

Strategy for the Development of Vaccines Against Chagas Disease

“…Immunizations with both genes also induced IgG2 immunoglobulin's and IFN-γ productions as well as lymph proliferation, indicating cell mediated immunity. In chronic stage, immunized dogs with DNA vaccines coding both genes challenged with T. cruzi still developed myocarditis with a partial protection from the experimental vaccines [54].…”