MyD88-dependent protective immunity elicited by adenovirus 5 expressing the surface antigen 1 from Toxoplasma gondii is mediated by CD8(+) T lymphocytes

Vaccine. 2011 Jun 15;29(27):4476-84. doi: 10.1016/j.vaccine.2011.04.044. Epub 2011 May 5.

Abstract

Toxoplasma gondii is an intracellular parasite widely spread around the world. The surface antigens (SAG) 1, 2 and 3 are the main proteins expressed on the surface of T. gondii tachyzoites. Replication-defective adenovirus serotype 5 (rAd5) is one of the most potent recombinant viral vectors for eliciting T cell-mediated immunity in mice and humans. Here we show that vaccination with rAd5 expressing SAG1 (AdSAG1), but neither SAG2 nor SAG3, induces protective immunity in the highly susceptible C57BL/6 mice challenged with T. gondii. Furthermore, we evaluated different immunological components involved on viral induced protective immunity. We observed that host protection elicited by AdSAG1 is highly dependent on IL-12, IFN-γ and CD8(+) T lymphocytes. Importantly, the induction of protective immunity (T cell-derived IFN-γ) was also dependent on Myeloid Differentiation Factor 88 (MyD88), and thus, likely to involve Toll-like Receptors. We conclude that protective parasite specific-CD8(+) T cells are elicited by a mechanism that involves MyD88-dependent induction of IL-12.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Antigens, Protozoan / metabolism
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / immunology
  • Myeloid Differentiation Factor 88 / metabolism*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Toxoplasma / genetics
  • Toxoplasma / immunology*
  • Toxoplasma / metabolism
  • Toxoplasmosis, Animal / immunology*
  • Toxoplasmosis, Animal / parasitology
  • Toxoplasmosis, Animal / prevention & control

Substances

  • Antigens, Protozoan
  • Antigens, Surface
  • Myeloid Differentiation Factor 88
  • Protozoan Proteins
  • Protozoan Vaccines