Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs

Background

Trypanosoma cruzi, the etiologic agent of Chagas Disease, isa major vector borne health problem in Latin America and an emerginginfectious disease in the United States.

Methods

We tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine(TcVac1) against experimental T. cruzi infection in acanine model. Dogs were immunized with antigen-encoding plasmids andcytokine adjuvants, and two weeks after the last immunization, challengedwith T. cruzi trypomastigotes. We measured antibodyresponses by ELISA and haemagglutination assay, parasitemia and infectivityto triatomines by xenodiagnosis, and performed electrocardiography andhistology to assess myocardial damage and tissue pathology.

Results

Vaccination 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, moderatelyenhanced CD8⁺ T cell proliferation and IFN-γ production,and suppression of phagocytes’ activity evidenced by decreasedmyeloperoxidase and nitrite levels. Subsequently, vaccinated dogs controlledthe acute parasitemia by day 37 pi (44 dpi in non-vaccinated dogs), andexhibited a moderate decline in infectivity to triatomines. TcVac1-immunizeddogs did not control the myocardial parasite burden and electrocardiographicand histopatholgic cardiac alterations that are the hallmarks of acuteChagas disease. During the chronic stage, TcVac1-vaccinated dogs exhibited amoderate decline in cardiac alterations determined by EKG andanatomo-/histo-pathological analysis whilechronically-infected/non-vaccinated dogs continued to exhibit severe EKGalterations.

Conclusions

Overall, these results demonstrated that TcVac1 provided a partial resistanceto T. cruzi infection and Chagas disease, and provide animpetus to improve the vaccination strategy against Chagas disease.