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Infection and Immunity, January 2004, p. 46-53, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.46-53.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immunotherapy of Trypanosoma cruzi Infection with DNA Vaccines in Mice

Eric Dumonteil,* Javier Escobedo-Ortegon, Norma Reyes-Rodriguez, Arletty Arjona-Torres, and Maria Jesus Ramirez-Sierra

Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico

Received 27 May 2003/ Returned for modification 26 July 2003/ Accepted 26 September 2003

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 104 parasites) as a model of acute infection, and then they were treated with two injections of 100 µg 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 102 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.

* Corresponding author. Mailing address: Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, Av. Itzaes 490 x 59, Centro, 97000, Mérida, Yucatán, Mexico. Phone: (999) 924-5910, ext. 118. Fax: (999) 923-6120. E-mail: oliver{at}tunku.uady.mx.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2004, p. 46-53, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.46-53.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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