Protective efficacy of two novel DNA vaccines expressing Toxoplasma gondii rhomboid 4 and rhomboid 5 proteins against acute and chronic toxoplasmosis in mice

Expert Rev Vaccines. 2015;14(9):1289-97. doi: 10.1586/14760584.2015.1061938. Epub 2015 Jun 25.

Abstract

Objectives: To evaluate the protective efficacy of two novel DNA vaccines expressing Toxoplasma gondii rhomboid 4 (ROM4) and rhomboid 5 (ROM5) proteins against acute and chronic toxoplasmosis.

Methods: DNA vaccines (pVAX-TgROM5 and pVAX-TgROM4) were constructed and their immunogenicity evaluated in Kunming mice.

Results: Mice vaccinated with pVAX-TgROM5 or pVAX-TgROM4 elicited strong Th1-type humoral and cellular responses, with higher level of IgG antibody titers (the predominance of IgG2a production), and increased levels of CD4(+) and CD8(+) T cells and cytokines IFN-γ, IL-2, IL-12 (p70) and IL-23. Mice vaccinated with pVAX-TgROM5 (11 days) showed a significantly longer survival time compared with controls (8 days) (p < 0.05) after lethal challenge. Brain cyst numbers of mice vaccinated with pVAX-TgROM5 and pVAX-TgROM4 reduced significantly (p < 0.05) (72.04 and 44.08%, respectively) compared with control groups after chronic challenge.

Conclusion: The pVAX-TgROM5 showed a better protective efficacy against acute and chronic toxoplasmosis compared to pVAX-TgROM4.

Keywords: DNA vaccine; ROM4; ROM5; Toxoplasma gondii; immune response; protective immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Brain / parasitology
  • Brain / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / blood
  • Mice
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Survival Analysis
  • Th1 Cells / immunology
  • Toxoplasma / genetics
  • Toxoplasma / immunology*
  • Toxoplasmosis, Animal / prevention & control*
  • Treatment Outcome
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Antibodies, Protozoan
  • Cytokines
  • Immunoglobulin G
  • Protozoan Proteins
  • Protozoan Vaccines
  • Vaccines, DNA
  • Peptide Hydrolases
  • ROM4 protein, Toxoplasma gondii
  • ROM5 protein, Toxoplasma gondii