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PLoS One. 2013;8(3):e59434. doi: 10.1371/journal.pone.0059434. Epub 2013 Mar 26.

TcVac3 induced control of Trypanosoma cruzi infection and chronic myocarditis in mice.

Author information

1
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.

Abstract

We characterized the immune responses elicited by a DNA-prime/MVA-boost vaccine (TcVac3) constituted of antigenic candidates (TcG2 and TcG4), shown to be recognized by B and T cell responses in Trypanosoma cruzi (Tc) infected multiple hosts. C57BL/6 mice immunized with TcVac3 elicited a strong antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1); and a robust antigen- and Tc-specific CD8(+)T cell response with type-1 cytokine (IFN-γ(+)TNF-α>IL-4(+)IL-10) and cytolytic effector (CD8(+)CD107a(+)IFN-γ(+)Perforin(+)) phenotype. The vaccine-induced effector T cells significantly expanded upon challenge infection and provided >92% control of T. cruzi. Co-delivery of IL-12 and GMCSF cytokine adjuvants didn't enhance the TcVac3-induced resistance to T. cruzi. In chronic phase, vaccinated/infected mice exhibited a significant decline (up to 70%) in IFN-γ(+)CD8(+)T cells, a predominance of immunoregulatory IL-10(+)/CD4(+)T and IL10(+)/CD8(+)T cells, and presented undetectable tissue parasitism, inflammatory infiltrate, and fibrosis in vaccinated/infected mice. In comparison, control mice responded to challenge infection by a low antibody response, mixed cytokine profile, and consistent activation of pro-inflammatory CD8(+)T cells associated with parasite persistence and pathologic damage in the heart. We conclude that TcVac3 elicited type-1 effector T cell immunity that effectively controlled T. cruzi infection, and subsequently, predominance of anti-inflammatory responses prevented chronic inflammation and myocarditis in chagasic mice.

PMID:
23555672
PMCID:
PMC3608676
DOI:
10.1371/journal.pone.0059434
[Indexed for MEDLINE]
Free PMC Article

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