Artículo
Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model
Autor
Aparicio Burgos, José Esteban; 224034
Zepeda Escobar, José Antonio; 370499
MONTES DE OCA JIMENEZ, ROBERTO; 14327
ESTRADA FRANCO, JOSE GUILLERMO; 225656
BARBABOSA PLIEGO, ALBERTO; 348264
OCHOA GARCIA, LAUCEL;x1225465
ALEJANDRE AGUILAR, RICARDO; 14804
RIVAS HERNANDEZ, NANCY; 232012
PEÑUELAS RIVAS, CLAUDIA GIOVANNA; 213291
VAL ARREOLA, MARGARITA;x1237316
Gupta, Shivali;#0000-0002-9598-7965
SALAZAR GARCIA, FELIX; 87532
Garg, Nisha;#0000-0002-3453-2369
VAZQUEZ CHAGOYAN, JUAN CARLOS; 120705
Aparicio Burgos, José Esteban
Zepeda Escobar, José Antonio
MONTES DE OCA JIMENEZ, ROBERTO
ESTRADA FRANCO, JOSE GUILLERMO
BARBABOSA PLIEGO, ALBERTO
OCHOA GARCIA, LAUCEL
ALEJANDRE AGUILAR, RICARDO
RIVAS HERNANDEZ, NANCY
PEÑUELAS RIVAS, CLAUDIA GIOVANNA; 213291
VAL ARREOLA, MARGARITA
Gupta, Shivali
SALAZAR GARCIA, FELIX
Garg, Nisha
VAZQUEZ CHAGOYAN, JUAN CARLOS
Institución
Resumen
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 GMCSF- 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. CONACYT PROY No. 156701 UAEM PROY No. 2381/2006U National Institutes of Health/National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/Pages/ default.aspx GRANT NUMBER (AI072538) NJG; American Heart Association http://www.heart.org/ HEARTORG/ GRANT NUMBER (0855059F) to NJG;