VP1 of Enterovirus 71 Protects Mice Against Enterovirus 71 and Coxsackievirus B3 in Lethal Challenge Experiment
VP1 of Enterovirus 71 Protects Mice Against Enterovirus 71 and Coxsackievirus B3 in Lethal Challenge Experiment
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在致死攻击实验中，肠道病毒 71 的 VP1 可保护小鼠免受肠道病毒 71 和柯萨奇病毒 B3 的侵害
DOI：
10.3389/fimmu.2019.02564
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发表时间：
2019-11-08
影响因子：
7.3
通讯作者：
Wang, Hui
中科院分区：
文献类型：
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作者：
Chen, Fang-Hong;Liu, Xiong;Wang, Hui
肠道病毒和柯萨奇病毒是导致全球手足口病(HFMD)暴发的主要病毒。多项研究表明，病毒包膜蛋白1(VP1)对不同基因型别的病毒株具有保护作用。然而，VP1在肠道病毒或柯萨奇病毒中是否具有交叉保护作用尚未得到深入研究。本研究将肠道病毒EV71(EV71)和柯萨奇病毒B3(CB3)的VP1基因分别插入表达载体pET22b(+)，构建成表达载体pEVP1或pCVP1，并转化到大肠杆菌BL21(DE3)中。成功表达了重组EVP1或CVP1蛋白，并得到了有效的纯化。然后，我们鉴定了EVP1和CVP1蛋白能有效地在小鼠体内产生特异性体液免疫和细胞免疫，并在小鼠模型中检测了VP1在EV71和CB3之间的交叉保护作用。结果表明，EVP1免疫小鼠可有效诱导抗CVP1的特异性Ig G和分泌型Ig A，免疫小鼠血清可中和CB3，平均效价为1：440。相比之下，在CVP1免疫的小鼠中没有检测到可测量的EV71中和抗体。然后，用EVP1或CVP1免疫其母亲的新生BALB/C小鼠，分别注射不同致死剂量的EV71或CB3。EVP1免疫组在CB3剂量为120LD50时的保护率为90%，而CVP1免疫组对EV71的15LD50的保护效果与BSA免疫组无显著差异。因此，EVP1是对抗肠道病毒71型和柯萨奇病毒B3引起的手足口病的一种很有前途的亚单位疫苗。
Enterovirus and Coxsackievirus are the major viruses that cause hand, foot, and mouth disease (HFMD) outbreaks worldwide. Several studies have shown the potential of viral envelope protein 1 (VP1) on providing protective effects from viral strains of different genotypes. However, whether VP1 has the cross-protection in Enteroviruses or Coxsackievirus has not been studied in-depth. In this study, the vp1 gene of Enterovirus 71 (EV71) and Coxsackievirus B3 (CB3) was inserted into the vector pET22b (+) to form the respective expression plasmids pEVP1 or pCVP1, and then transformed into Escherichia coli strain BL21 (DE3). The recombinant EVP1 or CVP1 protein was overexpressed successfully and effectively purified to homogeneity. Then, we identified that EVP1 and CVP1 protein could generate effectively specific humoral immunity and cellular immunity in mice, what's more, we determined the cross-protection of VP1 between EV71 and CB3 in a murine model. The results showed that immunization with EVP1 could effectively induce specific IgG and secretory IgA against CVP1 and the sera from EVP1-immunized mice could neutralize CB3 with mean titers 1:440. In contrast, no measurable neutralizing antibodies to EV71 were detected in CVP1-immunized mice. Then, newborn BALB/C mice, whose mother was immunized with EVP1 or CVP1, were administered with different lethal doses of EV71 or CB3. The EVP1 immunized group showed a 90% protective efficacy for a CB3 dosage of 120 LD50, but the CVP1 immunized group showed no significantly different protective efficacy against 15 LD50 of EV71 compared with the BSA immunized group. Hence, EVP1 is a promising subunit vaccine candidate against Enterovirus 71 and Coxsackievirus B3 caused HFMD.