Accelerated Evolution of H7N9 Subtype Influenza Virus under Vaccination Pressure

Abstract

No avian H7N9 outbreaks have occurred since the introduction of H7N9 inactivated vaccine in the fall of 2017. However, H7N9 is still prevalent in poultry. To surveil the prevalence, genetic characteristics, and antigenic changes of H7N9, over 7000 oropharyngeal and cloaca swab specimens were collected from live poultry markets and farms in 15 provinces of China from 2017 to 2019. A total of 85 influenza virus subtype H7N9 strains were isolated and 20 representative strains were selected for genetic analysis and antigenicity evaluation. Results indicated the decreased prevalence of low-pathogenic H7N9 strains while highly-pathogenic H7N9 strains became dominated since the introduction of vaccine. Phylogenetic analysis showed that strains from 2019 formed an independent small branch and were genetically distant to strains isolated in 2013–2018. Analysis of key amino acid sites showed that the virus strains may adapt to the host environment evolutionally through mutation. Our analysis predicted additional potential glycosylation sites for HA and NA genes in the 2019 strains. Sequence analysis of HA gene in strains isolated from 2018 to 2019 showed that there were an increased nucleotide substitution rate and an increased mutation rate in the first and second nucleotides of coding codons within the open reading frame. The hemagglutination inhibition (HI) assay showed that H7-Re1 and H7-Re2 exhibited a lower HI titer for isolates from 2019, while H7-Re3 and rLN79 showed a high HI titer. The protective effect of the vaccine decreased after 15 months of use. Overall, under vaccination pressure, the evolution of influenza virus subtype H7N9 has accelerated. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00383-x.

Spatiotemporal Associations and Molecular Evolution of Highly Pathogenic Avian Influenza A H7N9 Virus in China from 2017 to 2021

“…Only a small proportion of cases were detected in domestic ducks, pigeons, quails, and other wild birds in the first five epidemic waves [46][47][48][49]. Recent studies showed that the HP H7N9 virus was still detected in ducks and peacocks after wave 5 [16,17]. We found HP H7N9 AIVs primarily in chicken, especially from layers and partially from broilers, indicating that the HP H7N9 mainly infects the longer-lived layers or breeders in the farming industry.…”

“…Besides, sites 125/130 mutations induced a 5-fold difference in the neutralizing activity against the field virus [60]. Of note, the antigenicity of HP H7N9 AIV in recent years has drifted rapidly and significantly under intensive vaccination [10,12,[16][17][18]. Therefore, the antigenicity of the circulating HP H7N9 virus needs to be closely monitored, and the antigenic composition of vaccines needs to be updated as needed.…”

“…Although the prevalence of the HP H7N9 virus in poultry has been significantly reduced and human infection also has been largely eliminated [10,12,13], the H7N9 virus has not been eradicated from poultry [14,15]. Since the vaccines had been deployed to control HP H7N9, vaccine-evading variants invariably developed under vaccination pressure, resulting in the accelerated evolution of the HP H7N9 [16][17][18]. The persistent circulation of HP H7N9 is still a serious threat to public health and the poultry industry.…”

“…Subsequently, it quickly spread westward to adjacent provinces (Guangxi and Yunnan) and then to Northern China during the wave 5 outbreak [20]. Nonetheless, recent studies reported HP H7N9 AIVs in Central (Anhui [16]) and Southern (Yunnan and Guangdong [17]) China between 2017 and 2019, suggesting that HP H7N9 AIVs may not be only limited to Northern China after wave 6.…”

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

“…In particular, after the emergence of the highly pathogenic H7N9 avian influenza virus during the fifth wave, the H7N9 virus caused a sharp rise in human infection, resulting in 1,568 laboratory-confirmed cases and 616 deaths as of July 7, 2021 (http://www.fao.org/ag/againfo/programmes/en/empres/H7N9/ situation_update.html). More importantly, some novel biological features of the H7N9 virus, such as immune escape mutations and antigenic drift were discovered in H7N9 variants (2)(3)(4). Thus, there is still a possibility of an H7N9 pandemic outbreak.…”