Abstract
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.
Highlights
American trypanosomiasis (Chagas disease) is a disease of humans and caused by the protozoan Trypanosoma cruzi of the family trypanosomatidae [1]
We have shown the protective efficacy of amastigote surface proteins ASP-1 and ASP-2, and trypomastigote surface antigen TSA-1 as DNA vaccines in mice [8]
Dogs were confirmed free of T. cruzi infection by microscopic examination of blood smears and serological evaluation of anti-T. cruzi antibodies using an indirect haemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA) [15,18]
Summary
American trypanosomiasis (Chagas disease) is a disease of humans and caused by the protozoan Trypanosoma cruzi of the family trypanosomatidae [1]. Several investigators have shown the potential utility of T. cruzi surface antigens as vaccine candidates in murine experimental models [4,5](reviewed in [6,7]). We have shown the protective efficacy of amastigote surface proteins ASP-1 and ASP-2, and trypomastigote surface antigen TSA-1 as DNA vaccines in mice [8]. Vaccination with ASP-2 provided maximal immunity to T. cruzi infection in mice that was further enhanced by co-delivery of cytokine adjuvants [8]. When delivered as a DNA vaccine in mice, TcG1, TcVac Efficacy against Trypanosoma cruzi in Dogs. 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
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