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GENETIC VACCINATION AGAINST EXPERIMENTAL INFECTION WITH MYOTROPIC PARASITE STRAINS OF TRYPANOSOMA CRUZI.
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Abstract
In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replicationdefective
adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein
(ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite.
Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged withmyotropic parasite strains (Brazil
and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing themurine IL-12
gene improved the immune response and was essential for protective immunity elicited by the heterologous prime-boost regimen
in susceptiblemale mice against acute lethal infections with these parasites. The prophylactic or therapeutic vaccination of resistant
female mice led to a drastic reduction in the number of inflammatory infiltrates in cardiac and skeletal muscles during the chronic
phase of infection with either strain. Analysis of the electrocardiographic parameters showed that prophylactic vaccination reduced
the frequencies of sinus arrhythmia and atrioventricular block. Our results confirmed that prophylactic vaccination using the TS
and ASP-2 genes benefits the host against acute and chronic pathologies caused by T. cruzi and should be further evaluated for the
development of a veterinary or human vaccine against Chagas disease.
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