Martins Mathias, Joshi Lok R, Rodrigues Fernando S, Anziliero Deniz, Frandoloso Rafael, Kutish Gerald F, Rock Daniel L, Weiblen Rudi, Flores Eduardo F, Diel Diego G
Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil; Animal Disease Research and Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
Animal Disease Research and Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
Virology. 2017 Nov;511:229-239. doi: 10.1016/j.virol.2017.08.027. Epub 2017 Sep 9.
The parapoxvirus Orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. Here we describe the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). The RABV-G gene was inserted in the ORFV024 or ORFV121 gene loci, which encode for IMPs that are unique to parapoxviruses and inhibit activation of the NF-κB signaling pathway. The immunogenicity of the resultant recombinant viruses (ORFVRABV-G or ORFVRABV-G, respectively) was evaluated in pigs and cattle. Immunization of the target species with ORFVRABV-G and ORFVRABV-G elicited robust neutralizing antibody responses against RABV. Notably, neutralizing antibody titers induced in ORFVRABV-G-immunized pigs and cattle were significantly higher than those detected in ORFVRABV-G-immunized animals, indicating a higher immunogenicity of ORFV-based vectors in these animal species.
副痘病毒羊口疮病毒（ORFV）编码多种免疫调节蛋白（IMPs），这些蛋白可调节宿主的固有免疫和促炎反应，并且已被提议用作动物疫苗递送载体。在此，我们描述了两种表达狂犬病病毒（RABV）糖蛋白（G）的重组ORFV载体的构建和特性。RABV-G基因被插入到ORFV024或ORFV121基因位点，这两个位点编码副痘病毒特有的IMPs，可抑制NF-κB信号通路的激活。在猪和牛中评估了所得重组病毒（分别为ORFVRABV-G和ORFVRABV-G）的免疫原性。用ORFVRABV-G和ORFVRABV-G免疫目标物种引发了针对RABV的强烈中和抗体反应。值得注意的是，在ORFVRABV-G免疫的猪和牛中诱导的中和抗体滴度显著高于在ORFVRABV-G免疫的动物中检测到的滴度，表明基于ORFV的载体在这些动物物种中具有更高的免疫原性。
