title: Preventive and therapeutic DNA vaccination partially protect dogs against an infectious challenge with Trypanosoma cruzi.
abstract: American trypanosomiasis, or Chagas disease, is caused by Trypanosoma cruzi, and a vaccine would greatly improve disease control. While some studies in mice suggest that a vaccine is feasible, limited efficacy has been observed in dogs. We evaluated here the safety and efficacy of a DNA vaccine encoding TSA-1 and Tc24 antigens in a dog model of acute T. cruzi infection. Mongrel dogs were immunized with two doses of 500 μg of DNA vaccine, two weeks apart, and infected with T. cruzi (SylvioX10/4 strain) two weeks after the second vaccine dose. Another group of dogs was infected first and treated with the vaccine. Disease progression was monitored for up to 70 days post-infection. The vaccine did not induce any critical change in blood parameters, nor exacerbation of disease in vaccinated animals. On the contrary, it prevented anemia and a decrease in lymphocyte counts following T. cruzi infection in vaccinated dogs. Both preventive and therapeutic vaccination significantly reduced parasitemia, cardiac inflammation and cardiac parasite burden, and tended to reduce the development of cardiac arrhythmias. These results indicate that a preventive or therapeutic DNA vaccine encoding TSA-1 and Tc24 antigens is safe and may reduce both parasite transmission and the clinical progression of Chagas disease in vaccinated dogs. This DNA vaccine may thus be an excellent veterinary vaccine candidate. These data also further strengthen the feasibility of a Chagas disease vaccine for humans.
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán, 97000, Mérida, Yucatán, Mexico.
authors.forename: Israel A
authors.initials: IA
authors.lastname: Quijano-Hernández
authors.forename: Alejandro
authors.initials: A
authors.lastname: Castro-Barcena
authors.forename: Juan C
authors.initials: JC
authors.lastname: Vázquez-Chagoyán
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Bolio-González
authors.forename: Jaime
authors.initials: J
authors.lastname: Ortega-López
authors.forename: Eric
authors.initials: E
authors.lastname: Dumonteil
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D004285:Dogs; D006321:Heart / Q000469:parasitology; D059208:Parasite Load; D018512:Parasitemia / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA