Partial protective immunity against toxoplasmosis in mice elicited by recombinant Toxoplasma gondii malate dehydrogenase

Vaccine. 2016 Feb 10;34(7):989-94. doi: 10.1016/j.vaccine.2015.10.067. Epub 2015 Oct 27.

Abstract

Toxoplasma gondii can infect humans and wildlife, sometimes causing serious clinical presentations. Currently, no viable vaccine or effective drug strategies exist to prevent and control toxoplasmosis. T. gondii malate dehydrogenase (TgMDH) is a crucial enzyme in cellular redox reactions and has been shown to be an immunogenic compound that could be a potential vaccine candidate. Here, we investigate the protective efficacy of recombinant TgMDH (rTgMDH) against T. gondii infection in BALB/c mice. All mice were vaccinated via the nasal route. We determined the optimal vaccination dose by monitoring systemic and mucosal immune responses. The results showed that mice vaccinated with 30 μg of rTgMDH produced the highest antibody titers in serum, a strong lymphoproliferative response, marked increases in their levels of IL-2 and IFN-γ, and significantly greater levels of specific secretory IgA (sIgA) in mucosal washes. In addition, the vaccinated mice were orally challenged with tachyzoites of the virulent T. gondii RH strain 2 weeks after the final vaccination. Compared to the control group, we found that vaccination with rTgMDH increased the survival rate of infected mice by 47% and also significantly reduced the tachyzoite loads in their liver (by 58%) and brain (by 41%). Therefore, the rTgMDH protein triggers a strong systemic and mucosal immune response and provides partial protection against T. gondii infection.

Keywords: Malate dehydrogenase; Mice; Mucosal immunity; Nasal vaccine; Toxoplasma gondii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Protozoan / blood
  • Brain / parasitology
  • Cytokines / immunology
  • Female
  • Immunity, Mucosal
  • Immunoglobulin A, Secretory / immunology
  • Liver / parasitology
  • Malate Dehydrogenase / administration & dosage
  • Malate Dehydrogenase / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins / administration & dosage
  • Protozoan Proteins / immunology*
  • Protozoan Vaccines / immunology*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Toxoplasma / enzymology*
  • Toxoplasmosis, Animal / prevention & control*

Substances

  • Antibodies, Protozoan
  • Cytokines
  • Immunoglobulin A, Secretory
  • Protozoan Proteins
  • Protozoan Vaccines
  • Recombinant Proteins
  • Malate Dehydrogenase