The College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, 450002, China.
Henan Center for Animal Disease Control and Prevention, Zhengzhou, Henan, 450002, China.
Virus Res. 2015 Apr 2;201:8-15. doi: 10.1016/j.virusres.2015.02.010. Epub 2015 Feb 18.
A novel recombinant pseudorabies virus (PRV) expressing porcine circovirus type 2 (PCV2) capsid protein and IL-18 was constructed. The PCV2 open reading frame 2 (ORF2) and porcine IL-18 genes were amplified by PCR and then inserted into the PRV transfer vector (pG) to produce a recombinant plasmid (pGO18). Plasmid pGO18 was transfected into porcine kidney cell (PK15) pre-infected with PRV HB98 vaccine strain to generate a recombinant virus. The recombinant virus PRV-ORF2-IL18 was purified by green fluorescent plaque purification and the inserts were confirmed by PCR, enzyme digestion, sequencing, and Western blot. The humoral and cellular responses induced by the recombinant virus were assessed in mice. Mice (n=10) were immunized with PRV-ORF2-IL18, PRV-ORF2, PRV HB98, or inactivated PCV2. PRV-ORF2-IL18 elicited high titers of ELISA and serum neutralizing antibodies and strong cell-mediated immune responses in mice as indicated by anti-PCV2 ELISA, PRV-neutralizing assay, PCV2 specific lymphocyte proliferation assay, CD3(+), CD4(+) and CD8(+) T lymphocytes analysis, respectively. And PRV-ORF2-IL18 immunization protected mice against a lethal challenge of a virulent PRV Fa strain and significantly reduced the amount of PCV2 viremia. These results suggest an adjuvant effect of IL-18 on cellular immune responses. The recombinant virus might be an attractive candidate vaccine for preventing PCV2 and PRV infections in pigs.
构建了表达猪圆环病毒 2 型(PCV2)衣壳蛋白和白细胞介素 18(IL-18)的新型重组伪狂犬病病毒(PRV)。通过 PCR 扩增 PCV2 开放阅读框 2(ORF2)和猪 IL-18 基因,然后将其插入 PRV 转移载体(pG)中,构建重组质粒(pGO18)。将质粒 pGO18 转染到预先用 PRV HB98 疫苗株感染的猪肾细胞(PK15)中,产生重组病毒。通过绿色荧光斑纯化法纯化重组病毒 PRV-ORF2-IL18,并通过 PCR、酶切、测序和 Western blot 验证插入物。在小鼠中评估重组病毒诱导的体液和细胞反应。用 PRV-ORF2-IL18、PRV-ORF2、PRV HB98 或灭活的 PCV2 免疫小鼠(n=10)。PRV-ORF2-IL18 诱导 ELISA 和血清中和抗体滴度高,在小鼠中引起强烈的细胞介导免疫反应,如抗 PCV2 ELISA、PRV 中和测定、PCV2 特异性淋巴细胞增殖测定、CD3(+)、CD4(+)和 CD8(+)T 淋巴细胞分析分别。PRV-ORF2-IL18 免疫可保护小鼠免受强毒 PRV Fa 株的致死性攻击,并显著降低 PCV2 病毒血症量。这些结果表明 IL-18 对细胞免疫反应具有佐剂作用。该重组病毒可能是预防猪 PCV2 和 PRV 感染的有吸引力的候选疫苗。