Background
Trypanosoma cruzi, the etiologic agent of Chagas Disease, is
a major vector borne health problem in Latin America and an emerging
infectious disease in the United States.MethodsWe tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine
(TcVac1) against experimental T. cruzi infection in a
canine model. Dogs were immunized with antigen-encoding plasmids and
cytokine adjuvants, and two weeks after the last immunization, challenged
with T. cruzi trypomastigotes. We measured antibody
responses by ELISA and haemagglutination assay, parasitemia and infectivity
to triatomines by xenodiagnosis, and performed electrocardiography and
histology to assess myocardial damage and tissue pathology.ResultsVaccination with TcVac1 elicited parasite-and antigen-specific IgM and IgG
(IgG2>IgG1) responses. Upon challenge infection, TcVac1-vaccinated dogs,
as compared to non-vaccinated controls dogs, responded to T.
cruzi with a rapid expansion of antibody response, moderately
enhanced CD8+ T cell proliferation and IFN-γ production,
and suppression of phagocytes’ activity evidenced by decreased
myeloperoxidase and nitrite levels. Subsequently, vaccinated dogs controlled
the acute parasitemia by day 37 pi (44 dpi in non-vaccinated dogs), and
exhibited a moderate decline in infectivity to triatomines. TcVac1-immunized
dogs did not control the myocardial parasite burden and electrocardiographic
and histopatholgic cardiac alterations that are the hallmarks of acute
Chagas disease. During the chronic stage, TcVac1-vaccinated dogs exhibited a
moderate decline in cardiac alterations determined by EKG and
anatomo-/histo-pathological analysis while
chronically-infected/non-vaccinated dogs continued to exhibit severe EKG
alterations.ConclusionsOverall, these results demonstrated that TcVac1 provided a partial resistance
to T. cruzi infection and Chagas disease, and provide an
impetus to improve the vaccination strategy against Chagas disease.