Gatkowska Justyna, Wieczorek Marek, Dziadek Bożena, Dzitko Katarzyna, Dziadek Jarosław, Długońska Henryka
Department of Immunoparasitology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Łódź, Banacha 12/16, Poland.
Department of Neurobiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Łódź, Pomorska 141/143, Poland.
Vet Parasitol. 2018 Apr 30;254:82-94. doi: 10.1016/j.vetpar.2018.02.043. Epub 2018 Mar 1.
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.
本研究的目的是评估含选定重组弓形虫抗原（ROP2 + ROP4 + SAG1 + MAG1）与安全佐剂（MPL和明矾）联合使用的四价疫苗对雄性和雌性近交系小鼠的免疫原性和免疫保护活性，并确定其神经保护能力。所测试的抗原组合对脑囊肿形成提供了部分保护，尤其是对雄性小鼠（囊肿负荷减少72%）。在整个大脑以及与自然防御行为、情绪处理以及运动和感觉刺激整合相关的特定脑区均观察到囊肿负荷的降低。该疫苗引发了强烈的特异性免疫反应，且不受性别影响，其特征为细胞因子（IL-2、IFN-γ和IL-10）的抗原特异性体外合成以及全身IgG1和IgG2a免疫球蛋白的体内产生。在寄生虫攻击前进行免疫似乎会影响与弓形虫相关的行为和神经化学变化，尽管疫苗接种的影响在很大程度上取决于性别和感染后的时间。有趣的是，在接种疫苗并感染弓形虫的小鼠中，寄生虫诱导的对猫气味厌恶丧失出现了显著延迟（猫是该寄生虫的终末宿主）。在慢性寄生虫感染期间观察到，接种疫苗的雄性小鼠对猫科动物气味重新产生的吸引力与多巴胺代谢的增加相关。
