Toxoplasma gondii: Protective immunity against experimental toxoplasmosis induced by a DNA vaccine encoding the perforin-like protein 1
Toxoplasma gondii: Protective immunity against experimental toxoplasmosis induced by a DNA vaccine encoding the perforin-like protein 1
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DOI：
10.1016/j.exppara.2011.02.005
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发表时间：
2011-05-01
影响因子：
2.1
通讯作者：
Zhu, Xing-Quan
中科院分区：
文献类型：
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作者：
Yan, Hai-Kuo;Yuan, Zi-Guo;Zhu, Xing-Quan
弓形虫是一种重要的人畜共患寄生虫，感染世界上约三分之一的人口，引起先天性感染和眼病。T.弓形虫穿孔素样蛋白1（TgPLP 1）被认为与弓形虫的急性毒力有关。小鼠中的弓形虫，因此作为候选疫苗是有意义的。本研究构建了表达TgPLP 1的DNA疫苗，并在昆明种小鼠中进行了免疫应答的评价。将编码TgPLP 1的基因序列克隆到真核表达载体pVAX I中，肌肉注射免疫昆明小鼠。免疫后，我们用淋巴细胞增殖试验、细胞因子和抗体测定以及用1 × 10（3）个强毒T.弓形虫RH株结果表明，pVAX/TgPLP 1单独或与pVAX/IL-18联合应用可产生特异性抗TLA（T.弓形虫裂解抗原）抗体和特异性淋巴细胞增殖反应。共注射pVAX/IL-18显著增加IFN-γ和IL-2的产生。此外，攻击实验显示，与单独的pVAX/TgPLP 1（11.3 +/-0.9天）相比，pVAX/TgPLP 1与pVAX/IL-18的共免疫显著（P < 0.05）增加了免疫小鼠的存活时间（12.7 +/-1.2天）。这些结果表明，TgPLP 1是一个潜在的疫苗候选人针对弓形虫病，值得进一步评估在其他动物宿主。IL-18可增强TgPLP 1的免疫效果，延长免疫小鼠的存活时间。(C)2011 Elsevier Inc. All rights reserved.
Toxoplasma gondii is an important zoonotic parasite infecting about one third of the world population, causing congenital infections and eye disease. T. gondii perforin-like protein 1 (TgPLP1) is believed to be involved in the acute virulence of T. gondii in mice, and is therefore of interest as a vaccine candidate. In this study, we constructed a DNA vaccine expressing TgPLP1, and evaluated the immune response in Kunming mice. The gene sequence encoding TgPLP1 was inserted into the eukaryotic expression vector pVAX I, and Kunming mice were immunized intramuscularly with the plasmid. After immunization, we evaluated the immune response using lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged lethally with 1 x 10(3) tachyzoites of the virulent T. gondii RH strain. The results showed that pVAX/TgPLP1 alone or with pVAX/IL-18 developed specific anti-TLA (T. gondii lysate antigen) antibodies and specific lymphocyte proliferative responses. Co-injection of pVAX/IL-18 significantly increased the production of IFN-gamma and IL-2. Further, challenge experiments showed that co-immunization of pVAX/TgPLP1 with pVAX/IL-18 significantly (P < 0.05) increased survival time (12.7 +/- 1.2 days) of immunized mice, compared with pVAX/TgPLP1 alone (11.3 +/- 0.9 days). These results demonstrate that TgPLP1 is a potential vaccine candidate against toxoplasmosis, worth further evaluation in other animal hosts. IL-18 could enhance the immune effect of TgPLP1, prolonging the survival time of immunized mice. (C) 2011 Elsevier Inc. All rights reserved.