Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection attributed to dendritic cell stimulation.
Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection attributed to dendritic cell stimulation.
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DOI：
10.1016/j.vaccine.2017.10.052
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发表时间：
2017-12-15
期刊：
影响因子：
5.5
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Li Y;Wang G;Wang J;Man K;Yang Q
细胞减毒猪流行性腹泻病毒Zheedao08株为仔猪提供有效的免疫保护。浙江08比经典疫苗株CV777具有更高的刺激DC和激活T细胞增殖的能力。 S蛋白缺乏潜在的糖基化位点可能会引起更强的免疫反应。 2010年以来，猪流行性腹泻冠状病毒（PEDV）对全球猪肉产业造成了重大损害。然而，经典的 PEDV 疫苗株只能针对新出现的病毒株提供有限的保护。在本研究中，我们成功分离并减毒了PEDV流行毒株Zheede08，该毒株具有良好的细胞适应能力，并且在Vero E6细胞中感染后48小时即可产生高滴度。减毒病毒在仔猪中诱导高水平的病毒特异性中和抗体，直至免疫后120天，并在免疫后第14天受到新出现的病毒株攻击时提供完全保护。此外，还鉴定了该分离物激活树突状细胞（DC）的能力。用Zheed08处理24小时后，DC中IL-12和IFN-γ的表达水平更高。此外，基因组测序和系统发育分析揭示了Zhejiang08与2011年以后PEDV大流行分离株的主要抗原表位之间存在高度同源性。结合糖基化位点预测结果及其在S蛋白空间结构中的分布，得出的结论是，与CV777相比，所观察到的Zhejiang08更有效的宿主免疫反应可能与S蛋白的296个氨基酸中缺乏潜在的糖基化位点有关。总之，我们表明减毒病毒是一种有前途的候选疫苗。
Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection in piglets. Zhejiang08 has higher ability to stimulate DCs and activates T-cell proliferation than classical vaccine strain CV777. Potential glycosylation site lacking in S protein may cause the stronger immune response. Since 2010, the porcine epidemic diarrhea coronavirus (PEDV) has caused significant damage to the global pork industry. However, classical PEDV vaccine strains only provide limited protection against emerging strains. In this study, we successfully isolated and attenuated the PEDV epidemic strain Zhejiang08, which was characterized by good cell adaptation and high-titer production 48 h post infection in Vero E6 cells. The attenuated virus induced a high level of virus-specific neutralizing antibodies until 120 days after immunization in piglets and provided complete protection when challenged with an emerging virus strain on day 14 post immunization. Moreover, the capability to activate dendritic cells (DCs) of this isolate was identified. Higher expression levels of IL-12 and IFN-γ were recorded in DCs after treatment with Zhejiang08 for 24 h. Furthermore, genome sequencing and phylogenetic analysis revealed high homology between the main antigen epitopes of Zhejiang08 and PEDV pandemic isolates following 2011. Combining the glycosylation site prediction results and their distribution within the spatial structure of the S protein, led to the conclusion that the observed more effective host immune response of Zhejiang08 compared to CV777 was possibly associated with a lack of the potential glycosylation site in the 296 amino acids of the S protein. In summary, we illustrated that the attenuated virus represents a promising vaccine candidate.
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