Enhancement of the protective efficacy of a ROP18 vaccine against chronic toxoplasmosis by nasal route

Med Microbiol Immunol. 2017 Feb;206(1):53-62. doi: 10.1007/s00430-016-0483-9. Epub 2016 Oct 18.

Abstract

Infection with the parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. No vaccine is currently available, so the design of efficient vaccine strategies is still a topical question. In this study, we evaluated the immunoprophylactic potential of a T. gondii virulence factor, the rhoptry kinase ROP18, in a mouse model of chronic toxoplasmosis: first using a recombinant protein produced in Schneider insect cells adjuvanted with poly I:C emulsified in Montanide SV71 by a parenteral route or adjuvanted with cholera toxin by the nasal route and second using a DNA plasmid encoding ROP18 adjuvanted with GM-CSF ± IL-12 DNA. If both intranasal and subcutaneous recombinant ROP18 immunizations induced predominantly anti-ROP18 IgG1 antibodies and generated a mixed systemic Th1-/Th2-type cellular immune response characterized by the production of IFN-γ, IL-2, Il-10 and IL-5, only intranasal vaccination induced a mucosal (IgA) humoral response in intestinal washes associated with a significant brain cyst reduction (50 %) after oral challenge with T. gondii cysts. DNA immunization induced antibodies and redirected the cellular immune response toward a Th1-type response (production of IFN-γ and IL-2) but did not confer protection. These results suggest that ROP18 could be a component of a subunit vaccine against toxoplasmosis and that strategies designed to enhance mucosal protective immune responses could lead to more encouraging results.

Keywords: Immunoprophylaxis; Mucosal route; ROP18; T. gondii.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Administration, Intranasal
  • Animals
  • Antibodies, Protozoan / blood
  • Cholera Toxin / administration & dosage
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Immunity, Mucosal
  • Immunoglobulin A / analysis
  • Immunoglobulin G / blood
  • Injections, Subcutaneous
  • Mice, Inbred CBA
  • Oleic Acids / administration & dosage
  • Poly I-C / administration & dosage
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / immunology*
  • Protozoan Proteins
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Toxoplasmosis / prevention & control*
  • Treatment Outcome
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Cytokines
  • Immunoglobulin A
  • Immunoglobulin G
  • Oleic Acids
  • Protozoan Proteins
  • Protozoan Vaccines
  • Recombinant Proteins
  • Vaccines, DNA
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Cholera Toxin
  • Protein Serine-Threonine Kinases
  • ROP18 protein, Toxoplasma gondii
  • Poly I-C