Delivery of antigenic candidates by a DNA/MVA heterologous approach elicits effector CD8+T cell mediated immunity against Trypanosoma cruzi

Shivali Gupta, Nisha Garg

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In this study, we have characterized the immune mechanisms elicited by antigenic candidates, TcG2 and TcG4, delivered by a DNA-prime/MVA-boost approach, and evaluated the host responses to Trypanosoma cruzi infection in C57BL/6 mice. Immunization of mice with antigenic candidates elicited antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1) and CD8+T cells that exhibited type-1 cytolytic effector (CD8+CD107a+IFN-γ+Perforin+) phenotype. The extent of TcG2-dependent type 1 B and T cell immunity was higher than that noted in TcG4-immunized mice, and expanded accordingly in response to challenge infection with T. cruzi. The progression of chronic phase in immunized mice was associated with persistence of IgGs, 55-90% reduction in the frequency of proinflammatory (IFN-γ+ or TNF-α+) CD8+T cells, and an increase or emergence of immunoregulatory (IL-10+) CD4/CD8 T cells. The tissue parasitism, infiltration of inflammatory infiltrate, parasite persistence, and fibrosis were decreased by 82-92% in heart and skeletal muscle of immunized/chronically infected mice. Control mice exhibited a significantly low antibody response, consistent activation of effector CD8+T cells dominated by pro-inflammatory phenotype and mixed cytokine profile (IFN-γ+TNF-α>IL-4+IL-10), parasite persistence and pathologic damage in chagasic hearts. We conclude that delivery of TcG2 or TcG4 by DNA-rMVA approach elicits effective antibody and CD8+T cell mediated immunity against T. cruzi and Chagas disease. The emergence of type 2 cytokine and T cell response in chronic phase was indicative of prevention of clinical disease.

Original languageEnglish (US)
Pages (from-to)7179-7186
Number of pages8
JournalVaccine
Volume30
Issue number50
DOIs
StatePublished - Nov 26 2012

Fingerprint

Trypanosoma cruzi
Cellular Immunity
cell-mediated immunity
T-lymphocytes
T-Lymphocytes
DNA
mice
interleukin-10
Interleukin-10
Antibody Formation
Parasites
cytokines
heart
Cytokines
Phenotype
phenotype
parasites
Perforin
Chagas disease
antibodies

Keywords

  • Antigenic candidates
  • Chagas disease
  • DNA-prime/MVA-boost approach
  • Effector B and T cell responses
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Delivery of antigenic candidates by a DNA/MVA heterologous approach elicits effector CD8+T cell mediated immunity against Trypanosoma cruzi. / Gupta, Shivali; Garg, Nisha.

In: Vaccine, Vol. 30, No. 50, 26.11.2012, p. 7179-7186.

Research output: Contribution to journalArticle

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abstract = "In this study, we have characterized the immune mechanisms elicited by antigenic candidates, TcG2 and TcG4, delivered by a DNA-prime/MVA-boost approach, and evaluated the host responses to Trypanosoma cruzi infection in C57BL/6 mice. Immunization of mice with antigenic candidates elicited antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1) and CD8+T cells that exhibited type-1 cytolytic effector (CD8+CD107a+IFN-γ+Perforin+) phenotype. The extent of TcG2-dependent type 1 B and T cell immunity was higher than that noted in TcG4-immunized mice, and expanded accordingly in response to challenge infection with T. cruzi. The progression of chronic phase in immunized mice was associated with persistence of IgGs, 55-90{\%} reduction in the frequency of proinflammatory (IFN-γ+ or TNF-α+) CD8+T cells, and an increase or emergence of immunoregulatory (IL-10+) CD4/CD8 T cells. The tissue parasitism, infiltration of inflammatory infiltrate, parasite persistence, and fibrosis were decreased by 82-92{\%} in heart and skeletal muscle of immunized/chronically infected mice. Control mice exhibited a significantly low antibody response, consistent activation of effector CD8+T cells dominated by pro-inflammatory phenotype and mixed cytokine profile (IFN-γ+TNF-α>IL-4+IL-10), parasite persistence and pathologic damage in chagasic hearts. We conclude that delivery of TcG2 or TcG4 by DNA-rMVA approach elicits effective antibody and CD8+T cell mediated immunity against T. cruzi and Chagas disease. The emergence of type 2 cytokine and T cell response in chronic phase was indicative of prevention of clinical disease.",
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