Vaccine 28 (2010) 7414–7419 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Effect of a combination DNA vaccine for the prevention and therapy of Trypanosoma cruzi infection in mice: Role of CD4 + and CD8 + T cells Alberto Yairh Limon-Flores a , Rodrigo Cervera-Cetina a , Juan L. Tzec-Arjona a , Lorena Ek-Macias a , Gilma Sánchez-Burgos b , Maria J. Ramirez-Sierra a , J. Vladimir Cruz-Chan a , Nicole R. VanWynsberghe c , Eric Dumonteil a,d,∗ a Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico b Medical Research Branch, Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico c Laboratorio de Inmunología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico d Department of Tropical Medicine, Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA article info Article history: Received 13 June 2010 Received in revised form 26 August 2010 Accepted 31 August 2010 Available online 16 September 2010 Keywords: Chagas disease DNA vaccine Immunotherapy abstract Chagas disease is a major public health problem, with about 10 million infected people, and DNA vaccines are a promising alternative for the control of Trypanosoma cruzi, the causing agent of the disease. We tested here a new DNA vaccine encoding a combination of two leading parasite antigens, TSA-1 and Tc24, for the prevention and therapy of T. cruzi infection. Immunized Balb/c mice challenged by T. cruzi presented a significantly lower parasitemia and inflammatory cell density in the heart compared to control mice. Similarly, the therapeutic administration of the DNA vaccine was able to significantly reduce the parasitemia and inflammatory reaction in acutely infected Balb/c and C57BL/6 mice, and reduced cardiac tissue inflammation in chronically infected ICR mice. Therapeutic vaccination induced a marked increase in parasite-specific IFN producing CD4 + and CD8 + T cells in the spleen as well as an increase in CD4 + and CD8 + T cells in the infected cardiac tissue. In addition, some effect of the DNA vaccine could still be observed in CD4-knockout C57BL/6 mice, which presented a lower parasitemia and inflammatory cell density, but not in CD8-deficient mice, in which the vaccine had no effect. These results indicate that the activation of CD8 + T cells plays a major role in the control of the infection by the therapeutic DNA vaccine, and to a somewhat lesser extent CD4 + T cells. This observation opens interesting perspectives for the potentiation of this DNA vaccine candidate by including additional CD8 + T cell antigens/epitopes in future vaccine formulations. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and it is transmitted primarily by blood-feeding triatomine insect vectors. The disease affects an estimated 10 million peo- ple, with over 60 million being at risk of infection, mostly in Latin America [1]. About 30–40% of infected patients develop a chronic chagasic cardiomyopathy, which leads to cardiac failure and death. The important morbidity and mortality associated with Chagas dis- ease make it a major public health problem [1,2]. Current control measures to reduce transmission to humans are based on insect vector control strategies, as well as the screening ∗ Corresponding author at: Laboratorio de Parasitología, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Av. Itzaes 490 x 59, Centro, 97000, Mérida, Yucatán, Mexico. Tel.: +(52) 999 924 5910x118; fax: +(52) 999 923 6120. E-mail addresses: oliver@uady.mx, edumonte@tulane.edu (E. Dumonteil). of blood donors [3,4]. Therapeutic treatment of infected patients remains limited because current drugs are restricted to children and acute cases [5]. Thus, new alternatives are urgently needed to improve disease control [6]. After years of debate, there is now greater agreement that the parasite plays a central role in the pathogenesis of the disease, which strengthens the rationale for developing novel treatments as well as vaccines aimed at eliminating the parasite [7–9]. The potential of DNA vaccines for both prevention and therapy of T. cruzi infection has been demonstrated in several studies [10,11]. Indeed, preventive immunization with DNA vaccines encoding a variety of T. cruzi antigens can provide a significant control of a subsequent infection [12–15]. Such protection seems to rely par- ticularly on CD8+ cytotoxic T cells, and strong immunodominant epitopes for class I major histocompatibility complex (MHC) have been identified in parasite proteins from the trans-sialidase fam- ily [16–19]. Similarly, therapeutic immunization/immunotherapy following T. cruzi infection can also partially control the infection and reduce disease progression, and DNA vaccines encoding TSA- 0264-410X/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2010.08.104