Prophylactic efficacy of TcVac2 against Trypanosoma cruzi in mice

Shivali Gupta, Nisha Garg

Research output: Chapter in Book/Report/Conference proceedingChapter

39 Citations (Scopus)

Abstract

Background: Chagas disease is a major health problem in Latin America, and an emerging infectious disease in the US. Previously, we have screened the Trypanosoma cruzi sequence database by a computational/bioinformatics approach, and identified antigens that exhibited the characteristics of vaccine candidates. Methodology: We investigated the protective efficacy of a multi-component DNA-prime/protein-boost vaccine (TcVac2) constituted of the selected candidates and cytokine (IL-12 and GM-CSF) expression plasmids in a murine model. C57BL/6 mice were immunized with antigen-encoding plasmids plus cytokine adjuvants, followed by recombinant proteins; and two-weeks later, challenged with T. cruzi trypomastigotes. ELISA and flow cytometry were employed to measure humoral (antibody isotypes) and cellular (lymphocyte proliferation, CD4+ and CD8+ T cell phenotype and cytokines) responses. Myocardial pathology was evaluated by H&E and Masson's trichrome staining. Principal Findings: TcVac2 induced a strong antigen-specific antibody response (IgG2b>IgG1) and a moderate level of lymphocyte proliferation in mice. Upon challenge infection, TcVac2-vaccinated mice expanded the IgG2b/IgG1 antibodies and elicited a substantial CD8+ T cell response associated with type 1 cytokines (IFN-γ and TNF-α) that resulted in control of acute parasite burden. During chronic phase, antibody response persisted, splenic activation of CD8+ T cells and IFN-γ/TNFa cytokines subsided, and IL-4/IL-10 cytokines became dominant in vaccinated mice. The tissue parasitism, inflammation, and fibrosis in heart and skeletal muscle of TcVac2-vaccinated chronic mice were undetectable by histological techniques. In comparison, mice injected with vector or cytokines only responded to T. cruzi by elicitation of a mixed (type 1/type 2) antibody, T cell and cytokine response, and exhibited persistent parasite burden and immunopathology in the myocardium. Conclusion: TcVac2-induced activation of type 1 antibody and lymphocyte responses provided resistance to acute T. cruzi infection, and consequently, prevented the evolution of chronic immunopathology associated with parasite persistence in chagasic hearts.

Original languageEnglish (US)
Title of host publicationPLoS Neglected Tropical Diseases
Volume4
Edition8
DOIs
StatePublished - Aug 2010

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Trypanosoma cruzi
Cytokines
Antibody Formation
T-Lymphocytes
Lymphocytes
Antigens
Antibodies
Myocardium
Parasites
Plasmids
Vaccines
Immunoglobulin G
Emerging Communicable Diseases
Communicable Disease Control
Histological Techniques
Chagas Disease
Latin America
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Infection

ASJC Scopus subject areas

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

Cite this

Prophylactic efficacy of TcVac2 against Trypanosoma cruzi in mice. / Gupta, Shivali; Garg, Nisha.

PLoS Neglected Tropical Diseases. Vol. 4 8. ed. 2010. e797.

Research output: Chapter in Book/Report/Conference proceedingChapter

Gupta, Shivali ; Garg, Nisha. / Prophylactic efficacy of TcVac2 against Trypanosoma cruzi in mice. PLoS Neglected Tropical Diseases. Vol. 4 8. ed. 2010.
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