Vaccination with recombinant Toxoplasma gondii CDPK3 induces protective immunity against experimental toxoplasmosis

Acta Trop. 2019 Nov:199:105148. doi: 10.1016/j.actatropica.2019.105148. Epub 2019 Aug 16.

Abstract

Toxoplasma gondii, a ubiquitous and obligate intracellular pathogen, belonging to the phylum Apicomplexa, is capable of infecting a broad range of warm-blooded hosts including birds and mammals that is nearly worldwide. Preventive measures for toxoplasmosis are currently lacking and as such, development of novel vaccines is of urgent need. The plant-like calcium-dependent protein kinases (CDPKs) expressed by T. gondii, play important roles in cell invasion, gliding motility, egress and some other developmental processes, in which T. gondii CDPK3 (TgCDPK3) has been implicated as an important virulence factor. In this study, the immune protective function of recombinant TgCDPK3 (rTgCDPK3) against experimental toxoplasmosis in BALB/c were evaluated. We divided the mice into different dose groups of vaccines and all immunizations with purified rTgCDPK3 protein were injected by intramuscular at weeks 0, 2, and 4 in BALB/c mice. The rTgCDPK3 vaccine provided protection was correlated with the development of humoral and cellular immune responses demonstrated through the antigen-specific spleen cell proliferation, release of Th1 cytokines IFN-γ, and the production of the high titers of IgG antibody with a predominance of IgG2a over IgG1. Vaccination with rTgCDPK3 conferred partial protection against acute toxoplasmosis, as demonstrated by prolonged survival rate after lethal challenge. Additionally, the amount of brain tissues cysts in vaccinated mice led to 46.5% reduction compared with non-vaccinated ones. These data demonstrated that rTgCDPK3 inoculation prevents or attenuates the harmful influence of T. gondii infection, and it is a potential vaccine candidate against toxoplasmosis.

Keywords: Protective efficacy; Protein vaccine; T. gondii; TgCDPK3; Toxoplasmosis.

MeSH terms

  • Animals
  • Female
  • Interferon-gamma / analysis
  • Mice
  • Mice, Inbred BALB C
  • Protein Kinases / immunology*
  • Protozoan Vaccines / immunology*
  • Toxoplasma / immunology*
  • Toxoplasmosis, Animal / prevention & control*
  • Vaccination
  • Vaccines, Synthetic / immunology

Substances

  • Protozoan Vaccines
  • Vaccines, Synthetic
  • Interferon-gamma
  • Protein Kinases
  • calcium-dependent protein kinase