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Published on: January 27, 2019
Comparative evaluation of therapeutic DNA vaccines against Trypanosoma cruzi in mice
Gilma Sanchez-Burgos1, R Gabino Mezquita-Vega, Javier Escobedo-Ortegon
1Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr Hideyo Noguchi, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico.
Abstract:
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem in most of Latin America. A key priority is the development of new treatments, due to the poor efficacy of current ones. We report here the comparative evaluation of therapeutic DNA vaccines encoding various T. cruzi antigens. ICR mice infected with 500 parasites intraperitoneally were treated at 5 and 12 days postinfection with 20 microg of plasmid DNA encoding T. cruzi antigens TSA-1, TS, ASP-2-like, Tc52 or Tc24. Treatment with plasmid encoding TS and/or ASP-2-like antigens had no significant effect on parasitemia or survival. Treatment with Tc52 DNA significantly reduced parasitemia, as well as cardiac parasite burden, and improved survival, although myocarditis was not significantly affected. Finally, treatment with plasmids encoding Tc24 and TSA-1 induced the most complete control of disease as evidenced by significant reductions in parasitemia, mortality, myocarditis and heart parasite burden. These data demonstrate that therapeutic vaccine efficacy is dependent on the antigen and suggest that DNA vaccines encoding Tc24, TSA-1, and Tc52 represent the best candidates for further studies of a therapeutic vaccine against Chagas disease.
Insights
Developing new Chagas disease treatments is crucial. DNA vaccines targeting Trypanosoma cruzi antigens Tc24 and TSA-1 showed the most promise, significantly reducing parasite load, mortality, and heart damage in mice.
Area of Science:
- Immunology
- Parasitology
- Vaccine Development
Background:
- Chagas disease, caused by Trypanosoma cruzi, poses a significant public health challenge in Latin America.
- Current treatments for Chagas disease exhibit limited efficacy, necessitating the development of novel therapeutic strategies.
Purpose of the Study:
- To comparatively evaluate the therapeutic potential of DNA vaccines encoding different Trypanosoma cruzi antigens against Chagas disease.
- To identify the most effective antigens for developing a therapeutic DNA vaccine against Chagas disease.
Main Methods:
- ICR mice infected with Trypanosoma cruzi were treated with plasmid DNA encoding specific antigens (TSA-1, TS, ASP-2-like, Tc52, Tc24).
- Parasitemia, survival rates, cardiac parasite burden, and myocarditis were assessed post-treatment.
Main Results:
- DNA vaccines encoding TS and/or ASP-2-like antigens did not significantly impact parasitemia or survival.
- Treatment with Tc52 DNA reduced parasitemia and cardiac parasite burden, improving survival, but did not significantly affect myocarditis.
- DNA vaccines encoding Tc24 and TSA-1 demonstrated the most effective disease control, significantly reducing parasitemia, mortality, myocarditis, and heart parasite burden.
Conclusions:
- Therapeutic vaccine efficacy against Chagas disease is antigen-dependent.
- DNA vaccines encoding Tc24, TSA-1, and Tc52 are promising candidates for further development as therapeutic interventions for Chagas disease.
