Combination of CpG-oligodeoxynucleotides with recombinant ROP2 or GRA4 proteins induces protective immunity against Toxoplasma gondii infection

Exp Parasitol. 2011 Aug;128(4):448-53. doi: 10.1016/j.exppara.2011.04.004. Epub 2011 May 1.

Abstract

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) have been characterized as Th1-promoting immunopotentiators, an adjuvant activity desirable for vaccination against intracellular parasites like Toxoplasma gondii. In an attempt to find new antigen-adjuvant combinations that enhance the immunogenicity of antigen candidates for toxoplasma vaccines, we analyzed the extent of protection in mice immunized with ROP2 and GRA4 recombinant proteins when co-administered with CpG-ODN. Both GRA4+CpG-ODN and ROP2+CpG-ODN formulations were shown to induce a strong humoral Th1-biased response characterized by a high IgG(2a) to IgG(1) antibody ratio. Both vaccination regimens led to increased secretion of IFN-γ and IL-10, and negligible amounts of IL-4, upon specific re-stimulation of spleen cells from these groups of mice. After a non-lethal challenge with tissue cysts of a moderately virulent strain, only the brains from mice vaccinated with ROP2 or GRA4 in combination with CpG-ODN showed a significant reduction (63% and 62%, respectively) in their parasite load compared to the controls. The rate of protection obtained with GRA4+ROP2+CpG-ODN resulted equivalent (66%) to those achieved with the single antigens plus CpG-ODN. Taken together, these results indicate that CpG-ODN is an important candidate adjuvant for use in potential multicomponent anti-T. gondii vaccines for animals and humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antibodies, Protozoan / blood
  • Brain / parasitology
  • Cytokines / analysis
  • Female
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C3H
  • Oligodeoxyribonucleotides / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Protozoan Vaccines / immunology
  • Recombinant Proteins / immunology*
  • Spleen / immunology
  • Toxoplasma / immunology*
  • Toxoplasmosis, Animal / immunology
  • Toxoplasmosis, Animal / prevention & control*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • CPG-oligonucleotide
  • Cytokines
  • GRA4 protein, Toxoplasma gondii
  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • Protozoan Proteins
  • Protozoan Vaccines
  • ROP 2 protein, Toxoplasma gondii
  • Recombinant Proteins