title: Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.
abstract: Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.
authors: Escuela Superior de Apan-Universidad Autónoma del Estado de Hidalgo, Apan Hidalgo, México.
authors: José E
authors: JE
authors: Aparicio-Burgos
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: José A
authors: JA
authors: Zepeda-Escobar
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: Roberto Montes
authors: RM
authors: de Oca-Jimenez
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: José G
authors: JG
authors: Estrada-Franco
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: Alberto
authors: A
authors: Barbabosa-Pliego
authors: Laboratorio Estatal de Salud Pública del Instituto Salud del Estado de México, Toluca, México.
authors: Laucel
authors: L
authors: Ochoa-García
authors: Laboratorio de Entomología, Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, México City, México.
authors: Ricardo
authors: R
authors: Alejandre-Aguilar
authors: Laboratorio de Entomología, Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, México City, México.
authors: Nancy
authors: N
authors: Rivas
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: Giovanna
authors: G
authors: Peñuelas-Rivas
authors: Hospital General de Zona No. 2, Instituto Mexicano del Seguro Social, Irapuato, México.
authors: Margarita
authors: M
authors: Val-Arreola
authors: Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America.
authors: Shivali
authors: S
authors: Gupta
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: Felix
authors: F
authors: Salazar-García
authors: Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America; Department of Pathology, and Faculty of the Institute for Human Infection and Immunity, and the Sealy Center for Vaccine Development, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America.
authors: Nisha J
authors: NJ
authors: Garg
authors: Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México.
authors: Juan C
authors: JC
authors: Vázquez-Chagoyán
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000276:immunology; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12