College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin, 150030, China.
Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Xiangfang District, Harbin, 150069, China.
Virus Genes. 2020 Dec;56(6):734-748. doi: 10.1007/s11262-020-01799-5. Epub 2020 Oct 3.
Fowlpox virus (FPV) is used as a vaccine vector to prevent diseases in poultry and mammals. The insertion site is considered as one of the main factors influencing foreign gene expression. Therefore, the identification of insertion sites that can stably and efficiently express foreign genes is crucial for the construction of recombinant vaccines. In this study, we found that the insertion of foreign genes into ORF054 and the ORF161/ORF162 intergenic region of the FPV genome did not affect replication, and that the foreign genes inserted into the intergenic region were more efficiently expressed than when they were inserted into a gene. Based on these results, the recombinant virus rFPVNX10-NDV F-E was constructed and immune protection against virulent FPV and Newcastle disease virus (NDV) was evaluated. Tests for anti-FPV antibodies in the vaccinated chickens were positive within 14 days post-vaccination. After challenge with FPV102, no clinical signs of FP were observed in vaccinated chickens, as compared to that in the control group (unvaccinated), which showed 100% morbidity. Low levels of NDV-specific neutralizing antibodies were detected in vaccinated chickens before challenge. After challenge with NDV ck/CH/LHLJ/01/06, all control chickens died within 4 days post-challenge, whereas 5/15 vaccinated chickens died between 4 and 12 days post-challenge. Vaccination provided an immune protection rate of 66.7%, whereas the control group showed 100% mortality. These results indicate that the ORF161/ORF162 intergenic region of FPVNX10 can be used as a recombination site for foreign gene expression in vivo and in vitro.
禽痘病毒(FPV)被用作疫苗载体,以预防家禽和哺乳动物的疾病。插入位点被认为是影响外源基因表达的主要因素之一。因此,鉴定能够稳定和高效表达外源基因的插入位点对于重组疫苗的构建至关重要。在本研究中,我们发现外源基因插入 FPV 基因组的 ORF054 和 ORF161/ORF162 基因间区不影响复制,并且插入基因间区的外源基因表达效率高于插入基因时的表达效率。基于这些结果,构建了重组病毒 rFPVNX10-NDV F-E,并评估了其对强毒 FPV 和新城疫病毒(NDV)的免疫保护作用。接种鸡的抗 FPV 抗体检测在接种后 14 天内呈阳性。与对照组(未接种)相比,接种鸡在接种 FPV102 后没有观察到 FP 的临床症状,对照组的发病率为 100%。在攻毒前,接种鸡的 NDV 特异性中和抗体水平较低。攻毒 NDV ck/CH/LHLJ/01/06 后,所有对照鸡在攻毒后 4 天内全部死亡,而 5/15 只接种鸡在 4-12 天内死亡。接种提供了 66.7%的免疫保护率,而对照组的死亡率为 100%。这些结果表明,FPV NX10 的 ORF161/ORF162 基因间区可作为外源基因在体内和体外表达的重组位点。