The great clinical and economical impact of Toxoplasma gondii
infections makes the development of an effective
vaccine for controlling
toxoplasmosis an extremely important aim. In the presented study, we evaluate the protective and immunogenic properties of three recombinant
subunit vaccines composed of rROP2+rGRA4+rSAG1, rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1
proteins of T. gondii in an experimental
toxoplasmosis model in the C3H/HeJ and C57BL/6 mouse strains. All three
recombinant vaccines induced partial protection as measured by the reduction of brain
cyst burden following challenge with five tissue
cysts of the low virulence DX T. gondii strain. The level of protection was dependent on the
antigen composition of the
vaccine and the genetic background of the laboratory animals. The strongest protection against chronic
toxoplasmosis was induced in both C3H/HeJ and C57BL/6 mice by the mixture of rhoptry
proteins rROP2 and rROP4 combined with tachyzoite major
protein rSAG1. The average parasite burden in these groups of mice was reduced by 71% and 90%, respectively, compared to non-vaccinated mice. The observed protective effect was related to the
vaccine-induced cellular and humoral immune responses, as measured by the
antigen-induced release of the Th1
cytokines IFN-γ and
IL-2, the
antigen-stimulated proliferation of spleen cells of vaccinated animals in comparison to control animals and the development of systemic
antigen-specific
IgG1 and
IgG2a (C3H/HeJ) or IgG2c (C57BL/6)
antibodies. Our studies show that recombinant rROP2, rROP4, rGRA4 and rSAG1
antigens may be promising candidates for a
subunit vaccine against
toxoplasmosis. Additionally, we demonstrate that the ideal composition of
vaccine antigens can be equally effective in mice with different genetic backgrounds and variable levels of innate resistance to
toxoplasmosis, resulting in strong protection against T. gondii invasion.