Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination

Human infections with the H7N9 influenza virus have been eliminated in China through vaccination of poultry; however, the H7N9 virus has not yet been eradicated from poultry. Carefully analysis of H7N9 viruses in poultry that have sub-optimal immunity may provide a unique opportunity to witness the evolution of highly pathogenic avian influenza virus in the context of vaccination. Between January 2020 and June 2023, we isolated 16 H7N9 viruses from samples we collected during surveillance and samples that were sent to us for disease diagnosis. Genetic analysis indicated that these viruses belonged to a single genotype previously detected in poultry. Antigenic analysis indicated that 12 of the 16 viruses were antigenically close to the H7-Re4 vaccine virus that has been used since January 2022, and the other four viruses showed reduced reactivity with the vaccine. Animal studies indicated that all 16 viruses were nonlethal in mice, and four of six viruses showed reduced virulence in chickens upon intranasally inoculation. Importantly, the H7N9 viruses detected in this study exclusively bound to the avian-type receptors, having lost the capacity to bind to human-type receptors. Our study shows that vaccination slows the evolution of H7N9 virus by preventing its reassortment with other viruses and eliminates a harmful characteristic of H7N9 virus, namely its ability to bind to human-type receptors.

通过对家禽实施疫苗接种，我国已消除H7N9流感病毒引发的人类感染病例；但目前仍未从家禽种群中根除H7N9病毒。对处于亚最优免疫（sub-optimal immunity）状态家禽体内的H7N9病毒开展细致分析，或可提供独特契机，用以观察疫苗接种背景下高致病性禽流感病毒（Highly Pathogenic Avian Influenza Virus）的演化进程。2020年1月至2023年6月期间，研究团队从日常监测采集的样本以及送检的疾病诊断样本中，分离获得16株H7N9病毒。遗传分析结果显示，这些病毒均属于此前在家禽中检出的同一基因型。抗原性分析结果表明，16株病毒中的12株与2022年1月起投入使用的H7-Re4疫苗毒株抗原性相近，其余4株与该疫苗的反应活性有所降低。动物实验结果显示，16株病毒均对小鼠无致死性；其中4/6株病毒经鼻腔接种鸡只后，其毒力出现减弱。尤为关键的是，本研究检出的H7N9病毒仅能结合禽源型受体，已丧失结合人源型受体的能力。本研究证实，疫苗接种可通过阻断H7N9病毒与其他病毒发生基因重配（reassortment），延缓其演化进程，同时消除了该病毒结合人源型受体这一有害特性。