title: Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs.
abstract: BACKGROUND
  Trypanosoma cruzi, the etiologic agent of Chagas Disease, is a major vector borne health problem in Latin America and an emerging infectious disease in the United States.
  
  
  METHODS
  We tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine (TcVac1) against experimental T. cruzi infection in a canine model. Dogs were immunized with antigen-encoding plasmids and cytokine adjuvants, and two weeks after the last immunization, challenged with T. cruzi trypomastigotes. We measured antibody responses by ELISA and haemagglutination assay, parasitemia and infectivity to triatomines by xenodiagnosis, and performed electrocardiography and histology to assess myocardial damage and tissue pathology.
  
  
  RESULTS
  Vaccination with TcVac1 elicited parasite-and antigen-specific IgM and IgG (IgG2>IgG1) responses. Upon challenge infection, TcVac1-vaccinated dogs, as compared to non-vaccinated controls dogs, responded to T. cruzi with a rapid expansion of antibody response, moderately enhanced CD8(+) T cell proliferation and IFN-γ production, and suppression of phagocytes' activity evidenced by decreased myeloperoxidase and nitrite levels. Subsequently, vaccinated dogs controlled the acute parasitemia by day 37 pi (44 dpi in non-vaccinated dogs), and exhibited a moderate decline in infectivity to triatomines. TcVac1-immunized dogs did not control the myocardial parasite burden and electrocardiographic and histopatholgic cardiac alterations that are the hallmarks of acute Chagas disease. During the chronic stage, TcVac1-vaccinated dogs exhibited a moderate decline in cardiac alterations determined by EKG and anatomo-/histo-pathological analysis while chronically-infected/non-vaccinated dogs continued to exhibit severe EKG alterations.
  
  
  CONCLUSIONS
  Overall, these results demonstrated that TcVac1 provided a partial resistance to T. cruzi infection and Chagas disease, and provide an impetus to improve the vaccination strategy against Chagas disease.
authors.affiliation: Centro de Investigación y Estudios Avanzados, Universidad Autónoma de Estado de México, Toluca, México.
authors.forename: José E
authors.initials: JE
authors.lastname: Aparicio-Burgos
authors.forename: Laucel
authors.initials: L
authors.lastname: Ochoa-García
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Zepeda-Escobar
authors.forename: Shivali
authors.initials: S
authors.lastname: Gupta
authors.forename: Monisha
authors.initials: M
authors.lastname: Dhiman
authors.forename: José Simón
authors.initials: JS
authors.lastname: Martínez
authors.forename: Roberto Montes
authors.initials: RM
authors.lastname: de Oca-Jiménez
authors.forename: Margarita
authors.initials: M
authors.lastname: Val Arreola
authors.forename: Alberto
authors.initials: A
authors.lastname: Barbabosa-Pliego
authors.forename: Juan C
authors.initials: JC
authors.lastname: Vázquez-Chagoyán
authors.forename: Nisha Jain
authors.initials: NJ
authors.lastname: Garg
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics; D004195:Disease Models, Animal; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006386:Hemagglutination Tests; D007117:Immunization, Secondary / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000276:immunology / Q000517:prevention & control; D010957:Plasmids; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D016207:Cytokines; D016052:Protozoan Vaccines; D019444:Vaccines, DNA