Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Parasitol Res. 2013 Sep;112(9):3151-60. doi: 10.1007/s00436-013-3491-3. Epub 2013 Jun 20.
The current anti-Toxoplasma gondii drugs have many shortcomings and effective vaccines against T. gondii may contribute to the control of this pathogen. Pidotimod is a synthetic substance capable of stimulating both cellular and humoral immunity. To investigate the possible adjuvant effect of pidotimod on the immune response to T. gondii in Kunming mice induced by ultraviolet-attenuated T. gondii (UV-T.g), in this study, mice were immunized intraperitoneal (i.p.) with UV-T.g or UV-T.g co-administered with pidotimod (UV-T.g + PT). After infection or challenge by i.p. injection of 10(2) RH tachyzoites, the animal survival rate, parasite burden in peritoneal lavage fluids, liver histopathology, the level of serum anti-toxoplasma IgG antibody, and the mRNA expressions of IL-2, IFN-γ, and TNF-α from spleen analyzed using real-time PCR, were compared among different groups. The results showed that, compared with infected controls, infected mice treated with pidotimod had significantly increased survival rate and extended survival time, decreased parasite burden, improved liver histopathology, increased level of anti-toxoplasma IgG antibody, and increased mRNA expressions of Th1-type cytokine (IL-2, IFN-γ, and TNF-α) (P < 0.01), while mice vaccinated with UV-T.g and then challenged had even significantly increased survival rate and extended survival time, decreased parasite burden, improved liver histopathology, and increased mRNA expressions of Th1-type cytokines (IL-2, IFN-γ, and TNF-α) (P < 0.01); furthermore, vaccinated mice co-administered with pidotimod had even more lower parasite burden, milder liver histopathology, and higher levels of Th1-type cytokine and anti-toxoplasma IgG antibody (P < 0.01). Our data demonstrated that pidotimod in vivo could promote strong and specific humoral and cellular immune response to T. gondii challenge infection when co-administered with UV-attenuated T. gondii. It suggests that pidotimod may have the potential to be used as an effective vaccine adjuvant.
目前的抗弓形虫药物存在许多缺点，有效的弓形虫疫苗可能有助于控制这种病原体。匹多莫德是一种能够刺激细胞和体液免疫的合成物质。为了研究匹多莫德对紫外线减毒弓形虫（UV-T.g）诱导昆明小鼠弓形虫免疫的佐剂作用，本研究采用腹腔（i.p.）免疫法，用 UV-T.g 或 UV-T.g 联合匹多莫德（UV-T.g+PT）免疫小鼠。经腹腔注射 10（2）RH 速殖子感染或攻毒后，比较各组动物的存活率、腹腔灌洗液中的寄生虫负荷、肝组织病理学变化、血清抗弓形虫 IgG 抗体水平以及脾组织中 IL-2、IFN-γ 和 TNF-α 的 mRNA 表达。结果显示，与感染对照组相比，匹多莫德治疗组感染小鼠的存活率显著提高，存活时间延长，寄生虫负荷降低，肝组织病理学改善，抗弓形虫 IgG 抗体水平升高，Th1 型细胞因子（IL-2、IFN-γ 和 TNF-α）的 mRNA 表达增加（P<0.01）；而经 UV-T.g 免疫后再攻毒的小鼠，其存活率和存活时间进一步显著延长，寄生虫负荷降低，肝组织病理学改善，Th1 型细胞因子（IL-2、IFN-γ 和 TNF-α）的 mRNA 表达增加（P<0.01）；进一步给予匹多莫德治疗的小鼠，寄生虫负荷更低，肝组织病理学更轻，Th1 型细胞因子和抗弓形虫 IgG 抗体水平更高（P<0.01）。本研究结果表明，匹多莫德与紫外线减毒弓形虫联合应用可促进机体对弓形虫攻击感染产生强烈而特异的体液和细胞免疫应答，提示匹多莫德可能具有作为有效疫苗佐剂的潜力。
