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Immunotherapy of Trypanosoma cruzi infection with DNA vaccines in mice
Eric Dumonteil1, Javier Escobedo-Ortegon, Norma Reyes-Rodriguez
1Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico. oliver@tunku.uady.mx
Abstract:
The mechanisms involved in the pathology of chronic chagasic cardiomyopathy are still debated, and the controversy has interfered with the development of new treatments and vaccines. Because of the potential of DNA vaccines for immunotherapy of chronic and infectious diseases, we tested if DNA vaccines could control an ongoing Trypanosoma cruzi infection. BALB/c mice were infected with a lethal dose (5 x 10(4) parasites) as a model of acute infection, and then they were treated with two injections of 100 microg of plasmid DNA 1 week apart, beginning on day 5 postinfection. Control mice had high levels of parasitemia and mortality and severe cardiac inflammation, while mice treated with plasmid DNA encoding trypomastigote surface antigen 1 or Tc24 had reduced parasitemia and mild cardiac inflammation and >70% survived the infection. The efficacy of the immunotherapy also was significant when it was delayed until days 10 and 15 after infection. Parasitological analysis of cardiac tissue of surviving mice indicated that most mice still contained detectable parasite kinetoplast DNA but fewer mice contained live parasites, suggesting that there was efficient but not complete parasite elimination. DNA vaccine immunotherapy was also evaluated in CD1 mice infected with a low dose (5 x 10(2) parasites) as a model of chronic infection. Immunotherapy was initiated on day 70 postinfection and resulted in improved survival and reduced cardiac tissue inflammation. These results suggest that DNA vaccines have strong potential for the immunotherapy of T. cruzi infection and may provide new alternatives for the control of Chagas' disease.
Insights
DNA vaccines show promise for treating Chagas disease by reducing Trypanosoma cruzi infection and cardiac inflammation. This immunotherapy approach significantly improved survival rates in both acute and chronic infection models.
Area of Science:
- Immunology
- Parasitology
- Vaccinology
Background:
- The pathology of chronic Chagasic cardiomyopathy remains poorly understood, hindering the development of effective treatments and vaccines.
- Trypanosoma cruzi infection presents a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of DNA vaccines as a potential immunotherapy for controlling ongoing Trypanosoma cruzi infections.
- To assess the impact of DNA vaccine treatment on parasitemia, mortality, and cardiac inflammation in murine models of acute and chronic Chagas disease.
Main Methods:
- BALB/c mice with acute Trypanosoma cruzi infection received DNA plasmid injections encoding trypomastigote surface antigen 1 (Tc24) starting on day 5 postinfection.
- CD1 mice with chronic Trypanosoma cruzi infection received DNA vaccine immunotherapy starting on day 70 postinfection.
- Parasitemia, mortality, cardiac inflammation, and parasite DNA in cardiac tissue were assessed in treated and control groups.
Main Results:
- DNA vaccination significantly reduced parasitemia and cardiac inflammation, leading to >70% survival in acute infection models.
- Immunotherapy efficacy was observed even when treatment was delayed until days 10 and 15 postinfection.
- In chronic infection models, DNA vaccination improved survival and reduced cardiac tissue inflammation.
Conclusions:
- DNA vaccines demonstrate strong potential as an immunotherapy for Trypanosoma cruzi infection.
- This approach offers a promising new avenue for the control of Chagas disease.
- Further research into DNA vaccine strategies could lead to novel treatments for Chagas disease.
