Shi Lei, Hu Zenglei, Hu Jiao, Liu Dong, He Lihong, Liu Jiao, Gu Han, Gan Junji, Wang Xiaoquan, Liu Xiufan
Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.
Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China,
Avian Dis. 2019 Mar 1;63(1):61-67. doi: 10.1637/11965-090118-Reg.1.
In the fifth wave of the H7N9 avian influenza epidemic, highly pathogenic avian influenza (HPAI) A (H7N9) viruses have emerged and pose a great challenge to public health and the poultry industry. In addition, there are apparent genetic and antigenic variations between the classical H7N9 avian influenza virus and the newly-emerged H7N9 virus. Therefore, an antigenic-match vaccine is required for the prevention and control of H7N9 avian influenza in poultry in China. In this study, a recombinant Newcastle disease virus (NDV)-vectored vaccine expressing the HA derived from a prevailing HPAI H7N9 virus (GD15) was generated using reverse genetics. The recombinant virus (rAI4HA) showed virus yield and growth capacity in chicken embryos comparable to the parental virus (rAI4). Expression of the HA protein was detected in chicken embryo fibroblasts inoculated with rAI4HA. A chicken immunization study demonstrated that both rAI4HA and rAI4 induced similar anti-NDV hemagglutination inhibition (HI) antibody titers at weeks 2, 3, and 4 after a single immunization. However, rAI4HA-immunized chickens had a low seroconversion rate (20%) and negative HI titers against H7N9. Additionally, rAI4HA elicited high levels of H7N9-specifc IgY antibody as measured by ELISA. More importantly, the recombinant vaccine provided a complete protection against a lethal challenge with HPAI H7N9 virus and significantly inhibited virus shedding after a single immunization. Our results suggest that the recombinant NDV-vectored H7N9 vaccine expressing the antigenic-match HA can confer a complete protection against HPAI H7N9 challenge after a single immunization.
在H7N9禽流感疫情的第五波中,高致病性禽流感(HPAI)A(H7N9)病毒出现,对公共卫生和家禽业构成了巨大挑战。此外,经典H7N9禽流感病毒与新出现的H7N9病毒之间存在明显的基因和抗原变异。因此,中国需要一种抗原匹配疫苗来预防和控制家禽中的H7N9禽流感。在本研究中,利用反向遗传学构建了一种表达来自流行的HPAI H7N9病毒(GD15)的血凝素(HA)的重组新城疫病毒(NDV)载体疫苗。重组病毒(rAI4HA)在鸡胚中的病毒产量和生长能力与亲本病毒(rAI4)相当。在用rAI4HA接种的鸡胚成纤维细胞中检测到了HA蛋白的表达。一项鸡免疫研究表明,rAI4HA和rAI4在单次免疫后第2、3和4周诱导的抗NDV血凝抑制(HI)抗体滴度相似。然而,用rAI4HA免疫的鸡血清转化率较低(20%),且针对H7N9的HI滴度为阴性。此外,通过ELISA检测,rAI4HA诱导产生了高水平的H7N9特异性IgY抗体。更重要的是,该重组疫苗在单次免疫后对HPAI H7N9病毒的致死性攻击提供了完全保护,并显著抑制了病毒排出。我们的结果表明,表达抗原匹配HA的重组NDV载体H7N9疫苗在单次免疫后可对HPAI H7N9攻击提供完全保护。