DNA Vaccine Treatment in Dogs Experimentally Infected with Trypanosoma cruzi

Abstract

Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi, and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 T. cruzi strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.

The Case for the Development of a Chagas Disease Vaccine: Why? How? When?

“…An additional challenge is that the large majority of vaccine studies described above focus on mouse models, and the extent to which the strong vaccine immunogenicity and efficacy observed can be extrapolated to humans remains unknown. Studies in dogs have shown promise in reducing the T. cruzi parasite burden [ 86 , 87 , 88 , 89 , 90 ], but their limited scope does not provide sufficient evidence supporting vaccine efficacy to delay or prevent cardiac dysfunction. Infectiousness of dogs may nonetheless be reduced by vaccination [ 91 ].…”

In Search of the Vaccine Against Chagas Disease: A Tedious Road of More Than 100 Years

“…It should be noted that a limitation in a large part of the vaccine candidates evaluated is that they have been mainly tested in murine models, so it is unknown whether this observed efficacy is similar in humans. This leads to the use of other animal models, such as dogs [115], non-human primates [25], as well as the cellular response in chagasic patients [20], and mixed therapy trials have been carried out where low-dose chemotherapeutic treatment is combined with the application of vaccines [4], which in some cases it reduces heart disease [21] in others oxidative damage is controlled, observing a cardioprotective effect [116][117][118].…”

“…Vaccination is the cheapest strategy to prevent infectious diseases and a commercial Submit your Manuscript | www.austinpublishinggroup.com vaccine against ChD is not yet available. Multiple vaccine prototypes have been tested and have shown to be good candidates in terms of protection and with great advantages for their production and application [19][20][21][22][23][24]. During infection, the immune response that is generated against the parasite is not enough to neutralize and/ or eliminate it, this being the main factor in the persistence of the parasite as well as the development of the chronic phase of the disease; where the parasite load and the unbalance of oxidative stress generate the damage in the host tissue [25], therefore, the control of T. cruzi by activating the immune system during the acute phase of the disease would prevent the development of the pathology [26].…”

Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease

“…Both medications have potentially life-threatening adverse effects, resulting in repeated treatment pauses [ 14 , 15 , 16 ]. Previously, a study was conducted to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease [ 17 ]. Additionally, because several new vaccination applications have been proposed, most vaccines produced for dogs have been modified [ 17 ].…”

“…Previously, a study was conducted to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease [ 17 ]. Additionally, because several new vaccination applications have been proposed, most vaccines produced for dogs have been modified [ 17 ]. Its value associated with a prophylactic vaccination is clear and supported by several pre-clinical investigations, although specific performance and cost-effectiveness considerations must be addressed [ 16 ].…”