The Virulence-Related MYR1 Protein of Toxoplasma gondii as a Novel DNA Vaccine Against Toxoplasmosis in Mice
The Virulence-Related MYR1 Protein of Toxoplasma gondii as a Novel DNA Vaccine Against Toxoplasmosis in Mice
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弓形虫毒力相关 MYR1 蛋白作为抗小鼠弓形虫病的新型 DNA 疫苗
DOI：
10.3389/fmicb.2019.00734
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发表时间：
2019-04
影响因子：
5.2
通讯作者：
Lu Shaohong
中科院分区：
文献类型：
--
作者：
Zheng Bin;Ding Jianzu;Lou Di;Tong Qunbo;Zhuo Xunhui;Ding Haojie;Kong Qingming;Lu Shaohong
弓形虫造成严重的公共卫生问题，但目前尚无有效的治疗策略。 DNA 疫苗在这方面显示出了有希望的发现。 MYR1 是在弓形虫中发现的一种新毒力因子，可能具有作为 DNA 疫苗候选者的潜力。我们构建了重组真核质粒pVAX1-MYR1作为DNA疫苗，将其肌肉注射给BALB/c小鼠，并评估其免疫保护作用。 pVAX1-MYR1 免疫诱导了连续的 Th1 和 Th2 T 细胞应答，分别在免疫后 2 周和 6 周时出现高水平的 Th1 和混合 Th1/Th2 细胞因子。这些发现也得到了抗体测定的证实。此外，在免疫小鼠中还观察到抗原特异性淋巴细胞增殖、CD4+和CD8+T淋巴细胞、细胞毒性T淋巴细胞活性和细胞因子（IFN-γ、IL-12和IL-10）产生水平增加。这些发现表明 pVAX1-MYR1 刺激免疫小鼠的体液和细胞免疫反应。 IFN-γ 和 IL-12 产量的增加与 NF-κB 途径 T-bet 和 p65 基因表达的增加相关。然而，没有观察到IL-4水平的显着增加。与对照组小鼠相比，用pVAX1-MYR1免疫的小鼠的存活率也显着延长。基于上述所有发现，当前的研究提出pVAX1-MYR1可以诱导弓形虫特异性免疫反应，因此应被视为一种有前途的弓形体病候选疫苗。据我们所知，这是第一份评估基于 MYR1 的 DNA 疫苗针对弓形虫的免疫保护价值的报告。
Toxoplasma gondii causes serious public health problems, but there is no effective treatment strategy against it currently. DNA vaccines have shown promising findings in this regard. MYR1 is a new virulence factor identified in T. gondii that may have potential as a DNA vaccine candidate. We constructed a recombinant eukaryotic plasmid, pVAX1-MYR1, as a DNA vaccine, injected it intramuscularly into BALB/c mice, and evaluated its immunoprotective effects. pVAX1-MYR1 immunization induced a sequential Th1 and Th2 T-cell response, as indicated by high levels of Th1 and mixed Th1/Th2 cytokines at 2 and 6 weeks after immunization, respectively. These findings were corroborated by the antibody assays too. In addition, increased levels of antigen-specific lymphocyte proliferation, CD4+ and CD8+ T lymphocytes, cytotoxic T lymphocyte activity and cytokine (IFN-γ, IL-12, and IL-10) production were also observed in the immunized mice. These findings showed that pVAX1-MYR1 stimulated humoral and cellular immune responses in the immunized mice. The increased production of IFN-γ and IL-12 was correlated with increased expression of the T-bet and p65 genes of the NF-κB pathway. However, no significant increase was observed in the level of IL-4. The survival of mice immunized with pVAX1-MYR1 was also significantly prolonged compared with the control group mice. Based on all the above findings, the current study proposes that pVAX1-MYR1 can induce a T. gondii-specific immune response and should therefore be considered as a promising vaccine candidate against toxoplasmosis. To the best of our knowledge, this is the first report to evaluate the immunoprotective value of an MYR1-based DNA vaccine against T. gondii.
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影响因子：
11.3
作者：
Sullivan WJ Jr;Jeffers V
通讯作者：
Jeffers V
具有改变的血小板反应蛋白重复序列 (TgSPATR) 的弓形虫分泌蛋白作为针对 BALB/c 小鼠急性弓形虫病的新型 DNA 候选疫苗的免疫功效
影响因子：
5.2
作者：
Zheng B;Ding J;Chen X;Yu H;Lou D;Tong Q;Kong Q;Lu S
通讯作者：
Lu S
弓形虫的裂解周期：15年后。
影响因子：
10.5
作者：
Blader IJ;Coleman BI;Chen CT;Gubbels MJ
通讯作者：
Gubbels MJ
转录因子 T-bet 由多种途径诱导，并在 Th1 细胞反应期间阻止内源性 Th2 细胞程序。
影响因子：
32.4
作者：
Zhu J;Jankovic D;Oler AJ;Wei G;Sharma S;Hu G;Guo L;Yagi R;Yamane H;Punkosdy G;Feigenbaum L;Zhao K;Paul WE
通讯作者：
Paul WE
影响因子：
3.7
作者：
Belluco S;Mancin M;Conficoni D;Simonato G;Pietrobelli M;Ricci A
通讯作者：
Ricci A