Therapeutic DNA Vaccine against Trypanosoma cruzi Infection in Dogs

Abstract

Chagas' disease is an important health problem in most Latin American countries, and a concern in dog populations, which act as a reservoir. We showed in previous studies that a therapeutic DNA vaccine could partially control the pathology after Trypanosoma cruzi infection in mice, and this vaccine may represent an alternative treatment for Chagas' disease. Here we evaluated the therapeutic efficacy of this vaccine in experimentally infected dogs for up to 2 months after infection. Our results suggest that DNA vaccine treatment may affect the immune response and delay Chagas' disease progression in T. cruzi-infected dogs, and confirm the potential of this novel treatment.

Advances and challenges towards a vaccine against Chagas disease

“…Thus, clinical indicators such as EKG or echocardiography may provide valuable end-points to evaluate progressive cardiac damage and vaccine efficacy. 82,83 Also, such clinical indicators may be able to detect difference in disease progression rate within a reasonable time, as suggested by studies in dogs 66,67,84 and in patient follow-up evaluations. 82,83,85 In that respect, much can be learned from the current "BENEFIT" trial, which is evaluating the efficacy of drug treatment in chronicstage patients.…”

“…Importantly, the density of necrosis, inflammatory foci and amastigote nests (parasite burden) were increased in vaccinated dogs, as well as their mortality, suggesting a limited efficacy of this vaccine. 66 As in mice, the therapeutic administration of two doses of DNA vaccines encoding TSA-1 and Tc24 during the acute phase has also been tested in dogs and EKG recording indicated a decrease in the severity of cardiac arrythmias 67 (Quijano-Hernandez et al unpublished data). Importantly, this DNA vaccine can also reduce the density of amastigote nests, cardiac arrhythmias and mortality when used as a preventive vaccine in dogs, emphasizing the potential of this formualtion (Quijano-Hernandez et al unpublished data).…”

Evaluation of Clinical and Immunopathological Features of Different Infective Doses ofTrypanosoma cruziin Dogs during the Acute Phase

“…Electrocardiographic (ECG) recordings were performed at a 50 mm/s and 1 mV/cm sensitivity and bipolar and unipolar leads were recorded, with a Cardiofax, NIHON-KOHDEN [13], every two weeks after infection (PI) [14]. …”

Expression, purification, immunogenicity, and protective efficacy of a recombinant Tc24 antigen as a vaccine against Trypanosoma cruzi infection in mice

“…Indeed, 49 Please cite this article in press as: Martinez-Campos V, et al Expression, purification, immunogenicity, and protective efficacy of a recombinant Tc24 antigen as a vaccine against Trypanosoma cruzi infection in mice. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.07.017 these antigens, alone or in combination, have been found to be able to control a T. cruzi infection in a variety of mouse models [12][13][14][15] as well as in dogs [16,17], when used as DNA vaccines or as recombinant proteins [18,19].…”