Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs

José E. Aparicio-Burgos, Laucel Ochoa-García, José Antonio Zepeda-Escobar, Shivali Gupta, Monisha Dhiman, José Simón Martínez, Roberto Montes de Oca-Jiménez, Margarita Val Arreola, Alberto Barbabosa-Pliego, Juan C. Vázquez-Chagoyán, Nisha Garg

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1050
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number5
DOIs
StatePublished - May 2011

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DNA Vaccines
Trypanosoma cruzi
Dogs
Chagas Disease
DNA
Infection
Electrocardiography
Parasitemia
Immunoglobulin G
Antibody Formation
Vaccination
Xenodiagnosis
Emerging Communicable Diseases
Communicable Disease Control
Antigens
Latin America
Hemagglutination
Acute Disease
Phagocytes
Nitrites

ASJC Scopus subject areas

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

Cite this

Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs. / Aparicio-Burgos, José E.; Ochoa-García, Laucel; Zepeda-Escobar, José Antonio; Gupta, Shivali; Dhiman, Monisha; Martínez, José Simón; de Oca-Jiménez, Roberto Montes; Arreola, Margarita Val; Barbabosa-Pliego, Alberto; Vázquez-Chagoyán, Juan C.; Garg, Nisha.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 5, e1050, 05.2011.

Research output: Contribution to journalArticle

Aparicio-Burgos, JE, Ochoa-García, L, Zepeda-Escobar, JA, Gupta, S, Dhiman, M, Martínez, JS, de Oca-Jiménez, RM, Arreola, MV, Barbabosa-Pliego, A, Vázquez-Chagoyán, JC & Garg, N 2011, 'Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs', PLoS Neglected Tropical Diseases, vol. 5, no. 5, e1050. https://doi.org/10.1371/journal.pntd.0001050
Aparicio-Burgos, José E. ; Ochoa-García, Laucel ; Zepeda-Escobar, José Antonio ; Gupta, Shivali ; Dhiman, Monisha ; Martínez, José Simón ; de Oca-Jiménez, Roberto Montes ; Arreola, Margarita Val ; Barbabosa-Pliego, Alberto ; Vázquez-Chagoyán, Juan C. ; Garg, Nisha. / Testing the efficacy of a multi-component DNA-prime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 5.
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AU - Zepeda-Escobar, José Antonio

AU - Gupta, Shivali

AU - Dhiman, Monisha

AU - Martínez, José Simón

AU - de Oca-Jiménez, Roberto Montes

AU - Arreola, Margarita Val

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