Protection induced by recombinant vaccinia virus targeting the ROP4 of Toxoplasma gondii in mice

Exp Parasitol. 2025 Feb:269:108900. doi: 10.1016/j.exppara.2025.108900. Epub 2025 Jan 10.

Abstract

Toxoplasmosis is a parasitic disease affecting a significant portion of the global population, whose etiology can be attributed to the protozoan organism Toxoplasma gondii. Despite its public health importance, an efficacious vaccine to prevent human toxoplasmosis remains unavailable. To this end, we designed an experimental toxoplasmosis vaccine using recombinant vaccinia virus vectors (rVacv) expressing the T. gondii rhoptry protein 4 (ROP4) antigen and evaluated its efficacy in a murine model. Intranasal vaccination with ROP4-rVacvs induced parasite-specific serum antibody responses as early as 3 weeks post-immunization, with subsequent immunizations elevating antibody responses to a greater extent. When challenged with T. gondii ME49 strain, significantly enhanced levels of mucosal IgA antibodies were detected in the intestines of immunized mice. Additionally, ROP4-rVacv immunization ensured that T cells and germinal center B cell populations were retained at high levels. These immune responses mitigated the severity of neuroinflammation, reduced tissue cyst formation, and ensured the survival of immunized mice. Our findings indicate that ROP4-rVacv could be a promising toxoplasmosis vaccine candidate.

Keywords: Protection; Recombinant vaccinia virus; Rhoptry protein 4; Toxoplasma gondii; Vaccine.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antibodies, Protozoan / blood
  • Female
  • Genetic Vectors
  • Immunoglobulin A / analysis
  • Membrane Proteins* / genetics
  • Membrane Proteins* / immunology
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / immunology
  • Protozoan Vaccines* / immunology
  • Toxoplasma* / genetics
  • Toxoplasma* / immunology
  • Toxoplasmosis, Animal* / immunology
  • Toxoplasmosis, Animal* / prevention & control
  • Vaccines, Synthetic / immunology
  • Vaccinia virus* / genetics
  • Vaccinia virus* / immunology

Substances

  • Protozoan Vaccines
  • Antibodies, Protozoan
  • ROP4 protein, Toxoplasma gondii
  • Membrane Proteins
  • Protozoan Proteins
  • Vaccines, Synthetic
  • Immunoglobulin A