Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Viruses. 2022 Feb 11;14(2):376. doi: 10.3390/v14020376.
Since 2015, the outbreaks of hydropericardium-hepatitis syndrome (HHS) and inclusion body hepatitis (IBH) caused by the highly pathogenic serotype 4 fowl adenovirus (FAdV-4) and serotype 8 fowl adenovirus (FAdV-8), respectively, have caused huge economic losses to the poultry industry. Although several vaccines have been developed to control HHS or IBH, a recombinant genetic engineering vaccine against both FAdV-4 and FAdV-8 has not been reported. In this study, recombinant FAdV-4 expressing the fiber of FAdV-8b, designated as FA4-F8b, expressing fiber of FAdV-8b was generated by the CRISPR-Cas9 and homologous recombinant techniques. Infection studies in vitro and in vivo revealed that the FA4-F8b replicated efficiently in LMH cells and was also highly pathogenic to 2-week-old SPF chickens. Moreover, the inoculation of inactivated the FA4-F8b in chickens could not only induce highly neutralizing antibodies, but also provide efficient protection against both FAdV-4 and FAdV-8b. All these demonstrate that the inactivated recombinant FA4-F8b generated here can act as a vaccine candidate to control HHS and IBH, and FAdV-4 can be an efficient vaccine vector to deliver foreign antigens.
自 2015 年以来,由高致病性血清型 4 禽腺病毒(FAdV-4)和血清型 8 禽腺病毒(FAdV-8)分别引起的包涵体肝炎(IBH)和心包积液-肝炎综合征(HHS)的爆发,给家禽业造成了巨大的经济损失。尽管已经开发了几种疫苗来控制 HHS 或 IBH,但尚未报道针对 FAdV-4 和 FAdV-8 的重组基因工程疫苗。在本研究中,通过 CRISPR-Cas9 和同源重组技术,产生了表达 FAdV-8b 纤维的重组 FAdV-4,命名为 FA4-F8b。体外和体内感染研究表明,FA4-F8b 在 LMH 细胞中高效复制,并且对 2 周龄 SPF 鸡也具有高度致病性。此外,接种灭活的 FA4-F8b 不仅能在鸡体内诱导出高度中和抗体,还能对 FAdV-4 和 FAdV-8b 提供有效保护。所有这些都表明,这里产生的灭活重组 FA4-F8b 可以作为控制 HHS 和 IBH 的候选疫苗,而 FAdV-4 可以作为传递外源抗原的有效疫苗载体。