Identification of E2 with improved secretion and immunogenicity against CSFV in piglets
Identification of E2 with improved secretion and immunogenicity against CSFV in piglets
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DOI：
10.1186/s12866-020-1713-2
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发表时间：
2020-02-04
期刊：
影响因子：
4.2
通讯作者：
He, Fang
中科院分区：
文献类型：
--
作者：
Xu, Huiling;Wang, Yanli;He, Fang
背景猪瘟病毒（Classical Swine Fever Virus，CSFV）的爆发给养猪业造成了巨大的经济损失。疫苗接种是预防和控制该病的主要手段。由于减毒活疫苗不能在感染动物和免疫动物之间引起差异性免疫，亚单位疫苗被认为是预防和根除CSFV的替代候选物。亚单位疫苗在DIVA免疫原性和安全性方面具有优势。该技术由于产量低和多剂量和大剂量的高成本而受到限制。天然E2信号肽以前没有很好地定义。本研究的目的是通过信号肽和E2序列的选择，开发一种经济有效的抗CSFV的E2疫苗候选物。结果从浙江省猪瘟流行株中分离到一个新的E2序列（E2ZJ），该序列具有杆状病毒的分泌特性和较强的免疫原性。与所测试的任何其它信号肽相比，用所选择的信号肽SPZJ（SP23）诱导的E2分泌增加至少50%。此外，还鉴定出E2ZJ具有独特的抗原特性。与IFA中针对CSFV感染的免疫血清一样，E2ZJ在小鼠中比测试的其他E2型更早地引发CSFV抗体。此外，在28 dpi时，用E2ZJ检测到针对CSFV的中和抗体和CSFV抗体水平高于相同剂量的其他E2。此外，E2ZJ成功地在仔猪中引发中和免疫。5 μ g E2ZJ的单次剂量足以在仔猪中诱导针对CSFV的保护性抗体，并提供针对致死病毒攻击的100%保护。结论新的E2信号肽（SPZJ）引导的E2 ZJ能高效分泌，其免疫原性明显优于传统的E2疫苗。此外，5 μ g E2ZJ的单次剂量在仔猪中对CSFV有效。
Background Outbreaks of Classical swine fever virus (CSFV) cause significant economic losses in the swine industry. Vaccination is the major method to prevent and control the disease. As live attenuated vaccines fail to elicit differentiable immunity between infected and vaccinated animals, subunit vaccine was considered as an alternative candidate to prevent and eradicate CSFV. Subunit vaccines present advantages in DIVA immunogenicity and safety. The technology was limited due to the low yield and the high cost with multiple and large doses. The native E2 signal peptide has not been well defined before. Here, the aim of this study is to develop a cost-effective and efficacious E2 vaccine candidate against CSFV with signal peptide and E2 sequence selection. Results A novel CSFV E2 sequence (E2ZJ) was identified from an epidemic strain of Zhejiang for outstanding secretion in baculovirus and enhanced immunogenicity. E2 secretion induced with the selected signal peptide, SPZJ (SP23), increase at least 50% as compared to any other signal peptides tested. Besides, unique antigenic features were identified in E2ZJ. As indicated with immunized sera in IFA against CSFV infection, E2ZJ elicited CSFV antibodies at the earlier stage than other E2 types tested in mice. Moreover, higher level of neutralizing and CSFV antibodies against CSFV with E2ZJ was detected than other E2s with the same dosage at 28 dpi. Further, E2ZJ successfully elicited neutralizing immunity in piglets. A single dose of 5 mu g of E2ZJ was sufficient to induce protective antibodies against CSFV in piglets and provided 100% protection against lethal virus challenge. Conclusions Our studies provide evidence that E2ZJ guided by a novel E2 signal peptide (SPZJ) was efficiently secreted and presented significantly improved immunogenicity than conventional E2 vaccines. Moreover, a single dose of 5 mu g E2ZJ is efficacious against CSFV in piglets.