Immune Protection against Trypanosoma cruzi Induced by TcVac4 in a Canine Model

José E. Aparicio-Burgos, José A. Zepeda-Escobar, Roberto Montes de Oca-Jimenez, José G. Estrada-Franco, Alberto Barbabosa-Pliego, Laucel Ochoa-García, Ricardo Alejandre-Aguilar, Nancy Rivas, Giovanna Peñuelas-Rivas, Margarita Val-Arreola, Shivali Gupta, Felix Salazar-García, Nisha Garg, Juan C. Vázquez-Chagoyán

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0003625
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number4
DOIs
StatePublished - Apr 8 2015

Fingerprint

Trypanosoma cruzi
Canidae
Dogs
Immunoglobulin G
Parasites
Plasmids
Parasitemia
Chagas Disease
Vaccination
Xenodiagnosis
Infection
DNA Vaccines
DNA
Glutaral
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Infection Control
Antibody Formation
Immunity
Myocardium

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Aparicio-Burgos, J. E., Zepeda-Escobar, J. A., de Oca-Jimenez, R. M., Estrada-Franco, J. G., Barbabosa-Pliego, A., Ochoa-García, L., ... Vázquez-Chagoyán, J. C. (2015). Immune Protection against Trypanosoma cruzi Induced by TcVac4 in a Canine Model. PLoS Neglected Tropical Diseases, 9(4), [e0003625]. https://doi.org/10.1371/journal.pntd.0003625

Immune Protection against Trypanosoma cruzi Induced by TcVac4 in a Canine Model. / Aparicio-Burgos, José E.; Zepeda-Escobar, José A.; de Oca-Jimenez, Roberto Montes; Estrada-Franco, José G.; Barbabosa-Pliego, Alberto; Ochoa-García, Laucel; Alejandre-Aguilar, Ricardo; Rivas, Nancy; Peñuelas-Rivas, Giovanna; Val-Arreola, Margarita; Gupta, Shivali; Salazar-García, Felix; Garg, Nisha; Vázquez-Chagoyán, Juan C.

In: PLoS Neglected Tropical Diseases, Vol. 9, No. 4, e0003625, 08.04.2015.

Research output: Contribution to journalArticle

Aparicio-Burgos, JE, Zepeda-Escobar, JA, de Oca-Jimenez, RM, Estrada-Franco, JG, Barbabosa-Pliego, A, Ochoa-García, L, Alejandre-Aguilar, R, Rivas, N, Peñuelas-Rivas, G, Val-Arreola, M, Gupta, S, Salazar-García, F, Garg, N & Vázquez-Chagoyán, JC 2015, 'Immune Protection against Trypanosoma cruzi Induced by TcVac4 in a Canine Model', PLoS Neglected Tropical Diseases, vol. 9, no. 4, e0003625. https://doi.org/10.1371/journal.pntd.0003625
Aparicio-Burgos JE, Zepeda-Escobar JA, de Oca-Jimenez RM, Estrada-Franco JG, Barbabosa-Pliego A, Ochoa-García L et al. Immune Protection against Trypanosoma cruzi Induced by TcVac4 in a Canine Model. PLoS Neglected Tropical Diseases. 2015 Apr 8;9(4). e0003625. https://doi.org/10.1371/journal.pntd.0003625
Aparicio-Burgos, José E. ; Zepeda-Escobar, José A. ; de Oca-Jimenez, Roberto Montes ; Estrada-Franco, José G. ; Barbabosa-Pliego, Alberto ; Ochoa-García, Laucel ; Alejandre-Aguilar, Ricardo ; Rivas, Nancy ; Peñuelas-Rivas, Giovanna ; Val-Arreola, Margarita ; Gupta, Shivali ; Salazar-García, Felix ; Garg, Nisha ; Vázquez-Chagoyán, Juan C. / Immune Protection against Trypanosoma cruzi Induced by TcVac4 in a Canine Model. In: PLoS Neglected Tropical Diseases. 2015 ; Vol. 9, No. 4.
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