A recombinant pseudorabies virus expressing TgSAG1 protects against challenge with the virulent Toxoplasma gondii RH strain and pseudorabies in BALB/c mice

Microbes Infect. 2008 Oct;10(12-13):1355-62. doi: 10.1016/j.micinf.2008.08.002. Epub 2008 Aug 12.

Abstract

The major immunodominant surface antigen 1 (TgSAG1) of invasive tachyzoites is a vaccine candidate antigen for Toxoplasma gondii. In this study, we developed a recombinant pseudorabies virus (PRV) expressing TgSAG1 (rPRV/SAG1) based on the PRV vaccine strain Bartha K-61 by homologous recombination, in which partial PK and gG genes were deleted. The growth assay of rPRV/SAG1 showed that the recombinant virus can replicate in vitro as efficiently as PRV Bartha K-61, demonstrating that insertion of the TgSAG1 gene in the PK and gG locus of PRV does not affect the replication of PRV. All mice vaccinated with rPRV/SAG1 developed a high level of specific antibody responses against T. gondii lysate antigen (TLA), a strong increase of the splenocyte proliferative response, and significant levels of IFN-gamma and IL-2 production. And the immunization of mice with rPRV/SAG1 elicited strong cytotoxic T lymphocyte (CTL) responses in vitro. These results demonstrate that rPRV/SAG1 could induce significant humoral and cellular Th1 immune responses. Moreover, rPVR/SAG1 immunization induced partial protection (60%) against a lethal challenge with the highly virulent T. gondii RH strain, and neutralizing antibodies against PRV in a BALB/c mouse model. These results suggest that expression of protective antigens of T. gondii in PRV Bartha K-61 is a novel approach towards the development of a vaccine against both animal toxoplasmosis and pseudorabies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Antibodies, Viral / blood
  • Antigens, Protozoan* / genetics
  • Antigens, Protozoan* / immunology
  • Antigens, Protozoan* / metabolism
  • Herpesvirus 1, Suid* / genetics
  • Herpesvirus 1, Suid* / immunology
  • Herpesvirus 1, Suid* / metabolism
  • Herpesvirus 1, Suid* / pathogenicity
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / immunology
  • Protozoan Proteins* / metabolism
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology
  • Pseudorabies / immunology
  • Pseudorabies / prevention & control*
  • Pseudorabies / virology
  • Pseudorabies Vaccines / administration & dosage
  • Pseudorabies Vaccines / genetics
  • Pseudorabies Vaccines / immunology
  • Recombination, Genetic*
  • Toxoplasma / genetics
  • Toxoplasma / immunology
  • Toxoplasma / metabolism
  • Toxoplasma / pathogenicity
  • Toxoplasmosis, Animal / immunology
  • Toxoplasmosis, Animal / parasitology
  • Toxoplasmosis, Animal / prevention & control*
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology

Substances

  • Antibodies, Protozoan
  • Antibodies, Viral
  • Antigens, Protozoan
  • Protozoan Proteins
  • Protozoan Vaccines
  • Pseudorabies Vaccines
  • SAG1 antigen, Toxoplasma
  • Vaccines, DNA