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Assessment of the antigenic and neuroprotective activity of the subunit anti-Toxoplasma vaccine in T. gondii experimentally infected mice

Gatkowska, Justyna, Wieczorek, Marek, Dziadek, Bożena, Dzitko, Katarzyna, Dziadek, Jarosław, Długońska, Henryka
Veterinary parasitology 2018 v.254 pp. 82-94
adjuvants, alum, antigens, brain, cats, defensive behavior, definitive hosts, dopamine, females, immune response, immunoglobulin G, interferon-gamma, interleukin-10, interleukin-2, males, metabolism, mice, neuroprotective effect, odors, parasites, smell, vaccination, vaccines
The aim of this study was to evaluate the immunogenic and immunoprotective activities and to determine the neuroprotective capacity of the tetravalent vaccine containing selected recombinant T. gondii antigens (ROP2 + ROP4 + SAG1 + MAG1) administered with safe adjuvants (MPL and alum) using male and female inbred mice. The tested antigenic combination provided partial protection against brain cyst formation, especially in males (reduction in cyst burden by 72%). The decrease in cyst burden was observed for the whole brain as well as for specified brain regions associated with natural defensive behaviors, emotion processing and integration of motor and sensory stimuli. The vaccine triggered a strong, specific immune response, regardless of sex, which was characterized by the antigen-specific in vitro synthesis of cytokines (IL-2, IFN-γ and IL-10) and in vivo production of systemic IgG1 and IgG2a immunoglobulins. Immunization prior to the parasite challenge seemed to influence T. gondii – associated behavioral and neurochemical changes, although the impact of vaccination strongly depended on sex and time post-infection. Interestingly, in the vaccinated and T. gondii infected mice there was a significant delay in the parasite-induced loss of aversion toward cat smell (cats are the definitive hosts of the parasite). The regained attraction toward feline scent in vaccinated males, observed during chronic parasite invasion, correlated with the increase in the dopamine metabolism.