Immunogenicity of a recombinant parapoxvirus expressing the spike protein of Porcine epidemic diarrhea virus
Immunogenicity of a recombinant parapoxvirus expressing the spike protein of Porcine epidemic diarrhea virus
复制标题
DOI：
10.1099/jgv.0.000586
复制
发表时间：
2016-10-01
影响因子：
3.8
通讯作者：
Diel, Diego G.
中科院分区：
文献类型：
--
作者：
Hain, Kyle S.;Joshi, Lok R.;Diel, Diego G.
副痘病毒Orf病毒(ORFV)在放养和非放养动物中具有免疫调节作用，长期以来一直被公认。构建了表达猪流行性腹泻病毒S全长S蛋白的重组ORFV，并对其免疫原性和免疫保护效果进行了评价。PEDV S被插入到ORFV121基因座上，ORFV121是一个免疫调节基因，它抑制了核因子-kappaB信号通路的激活，并参与了ORFV在自然宿主中的毒力。重组ORFV-PEDV-S病毒在体外细胞培养中高效稳定表达PEDV S蛋白。用重组ORFV-PEDV-S肌肉注射免疫3周龄仔猪，可产生较强的血清免疫球蛋白G、IgA和中和抗体。此外，重组ORFV-PEDV-S病毒的IM免疫保护了猪流行性腹泻的临床症状，并减少了攻击性感染时粪便中的病毒排放。这些结果表明，ORFV121基因座适合作为ORFV病毒载体表达和传递外源基因的插入位点。此外，这些结果还为ORFV作为猪肠道病毒病疫苗输送载体的潜力提供了证据。本研究对今后猪ORFV载体疫苗的研制具有重要意义。
The parapoxvirus Orf virus (ORFV), has long been recognized for its immunomodulatory properties in permissive and non-permissive animal species. Here, a new recombinant ORFV expressing the full-length spike (S) protein of Porcine epidemic diarrhea virus (PEDV) was generated and its immunogenicity and protective efficacy were evaluated in pigs. The PEDV S was inserted into the ORFV121 gene locus, an immunomodulatory gene that inhibits activation of the NF-kappa B signalling pathway and contributes to ORFV virulence in the natural host. The recombinant ORFV-PEDV-S virus efficiently and stably expressed the PEDV S protein in cell culture in vitro. Three intramuscular (IM) immunizations with the recombinant ORFV-PEDV-S in 3-week-old pigs elicited robust serum IgG, IgA and neutralizing antibody responses against PEDV. Additionally, IM immunization with the recombinant ORFV-PEDV-S virus protected pigs from clinical signs of porcine epidemic diarrhoea (PED) and reduced virus shedding in faeces upon challenge infection. These results demonstrate the suitability of ORFV121 gene locus as an insertion site for heterologous gene expression and delivery by ORFV-based viral vectors. Additionally, the results provide evidence of the potential of ORFV as a vaccine delivery vector for enteric viral diseases of swine. This study may have important implications for future development of ORFV-vectored vaccines for swine.