Synergy of mIL-21 and mIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice
Synergy of mIL-21 and mIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice
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DOI：
10.1016/j.vaccine.2014.03.042
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发表时间：
2014-05-23
期刊：
影响因子：
5.5
通讯作者：
Zhu, Xing-Quan
中科院分区：
文献类型：
--
作者：
Li, Zhong-Yuan;Chen, Jia;Zhu, Xing-Quan
用弓形虫T.以弓形虫MIC 8（TgMIC 8）为模型。从昆明小鼠脾组织中克隆了mIL-21和mIL-15，分别构建了pVAX/mIL-15、pVAX/mIL-21和pVAX/mIL-21/mIL-15真核表达质粒。在存在或不存在这些细胞因子的情况下用pVAX/TgMIC 8免疫后，使用淋巴细胞增殖测定、细胞因子和血清抗体测量、淋巴细胞上的流式细胞术表面标记和对急性和慢性T.弓形虫感染单独接受pVAX/TgMIC 8的小鼠产生了强烈的体液免疫应答和Th 1型细胞免疫应答，并且与所有对照相比显示出CD 4+和CD 8 + T细胞的增加。与pVAX/TgMIC 8相比，将pVAX/mIL-21加入到pVAX/TgMIC 8中仅导致体液和细胞免疫应答的轻微增加，并且该免疫应答低于由pVAX/mIL-15与pVAX/TgMIC 8组合诱导的免疫应答。与所有对照相比，pVAX/mIL-21/mIL-15与pVAX/TgMIC 8的联合施用在所有组中引发最强的体液和细胞免疫应答，导致针对急性感染的存活时间显著增加，组织囊肿显著减少。mIL-21和mIL-15的协同作用可促进T细胞DNA疫苗诱导的特异性体液和细胞免疫应答。小鼠弓形虫感染。(C)2014爱思唯尔有限公司版权所有。
The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated with DNA vaccine against acute and chronic Toxoplasma gondii infection in mice was investigated using T. gondii MIC8 (TgMIC8) as a model. We cloned mIL-21 and mIL-15 from splenic tissues of Kunming mice, and constructed eukaryotic plasmid pVAX/mIL-15, pVAX/mIL-21, and pVAX/mIL-21/mIL-15, respectively. After immunizing with pVAX/TgMIC8 in the presence or absence of these cytokines, immune responses were analyzed using lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes and protection against acute and chronic T. gondii infection. Mice receiving pVAX/TgMIC8 alone developed a strong humoral responses and Th1 type cellular immune responses, and showed an increase of CD4+ and CD8+ T cells compared with all the controls. Adding pVAX/mIL-21 to pVAX/TgMIC8 compared to pVAX/TgMIC8 resulted in only a slight increase in humoral and cellular immune responses, and this immune response was lower than that induced by the pVAX/mIL-15 combined with pVAX/TgMIC8. Co-administration of pVAX/mIL-21/mIL-15 combined with pVAX/TgMIC8 elicited the strongest humoral and cellular immune responses among all the groups, leading to significantly increased survival time against acute infection and the significant reduction of tissue cysts, compared to all the controls. Synergy of mIL-21 and mIL-15 can facilitate specific humoral as well as cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice. (C) 2014 Elsevier Ltd. All rights reserved.