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 (ORFV^∆024RABV-G or ORFV^∆121RABV-G, respectively) was evaluated in pigs and cattle. Immunization of the target species with ORFV^∆024RABV-G and ORFV^∆121RABV-G elicited robust neutralizing antibody responses against RABV. Notably, neutralizing antibody titers induced in ORFV^∆121RABV-G-immunized pigs and cattle were significantly higher than those detected in ORFV^∆024RABV-G-immunized animals, indicating a higher immunogenicity of ORFV^Δ121-based vectors in these animal species.

副痘病毒Orf病毒（ORFV）编码几种免疫调节蛋白（IMP），这些蛋白调节宿主的先天性和促炎性反应，并已被提议作为用于动物物种的疫苗递送载体。在这里，我们描述了两个表达狂犬病病毒（RABV）糖蛋白（G）的重组ORFV载体的构建和表征。将RABV-G基因插入ORFV024或ORFV121基因位点，该位点编码副痘病毒独有的IMP，并抑制NF-κB信号通路的激活。重组病毒的免疫原性（ORFV ^{∆024 RABV} -G或ORFV ^∆121分别在猪和牛中评估了RABV-G）。用ORFV ^{∆024 RABV} -G和ORFV ^{∆121 RABV} -G免疫目标物种可引发针对^RABV的强大中和抗体反应。值得注意的是，在^{ORFVΔ121RABV} -G免疫的猪和牛中诱导的中和抗体滴度显着高于在^{ORFVΔ024RABV} -G免疫的动物中检测到的中和抗体滴度，表明这些动物物种中基于^ORFVΔ121的载体具有更高的免疫原性。