Ecology of avian influenza viruses in migratory birds wintering within the Yangtze River wetlands.

Migratory birds are considered natural reservoirs of avian influenza A viruses (AIVs). To further our viral ecology knowledge and understand the subsequent risk posed by wild birds, we conducted a 4-year surveillance study of AIVs in the bird wintering wetlands of the Yangtze River, China. We collected over 8000 samples and isolated 122 AIV strains. Analyses were then carried out with 108 novel sequenced genomes and data were deposited in GISAID and other public databases. The results showed that the Yangtze River wintering wetlands functioned as a mixing ground, where various subtypes of AIVs were detected harboring a high diversity of nucleotide sequences; moreover, a portion of AIV gene segments were persistent inter-seasonally. Phylogenetic incongruence presented complex reassortment events and distinct patterns among various subtypes. In addition, we observed that viral gene segments in wintering wetlands were closely related to known North American isolates, indicating that intercontinental gene flow occurred. Notably, highly pathogenic H5 and low pathogenic H9 viruses, which usually circulate in poultry, were found to have crossed the poultry/wild bird interface, with the viruses introduced to wintering birds. Overall, this study represented the largest AIV surveillance effort of wild birds within the Yangtze River wintering wetlands. Surveillance data highlighted the important role of wintering wild birds in the ecology of AIVs and may enable future early warnings of novel AIV emergence.

Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses.

H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses require the development of cross-protective vaccine candidates. In this study, a methodology called computationally optimized broadly reactive antigen (COBRA) was used to develop four consensus H7 antigens (CH7-22, CH7-24, CH7-26, and CH7-28). In vitro experiments confirmed the binding of monoclonal antibodies to the head and stem domains of cell surface-expressed consensus HAs, indicating display of their antigenicity. Immunization with DNA vaccines encoding the four antigens was evaluated in a mouse model. Broadly reactive antibodies against H7 viruses from Eurasian and North American lineages were elicited and detected by binding, inhibition, and neutralizing analyses. Further infection with Eurasian H7N9 and North American H7N3 virus strains confirmed that CH7-22 and CH7-24 conferred the most effective protection against hetero-lethal challenge. Our data showed that the consensus H7 vaccines elicit a broadly reactive, protective response against Eurasian and North American lineage H7 viruses, which are suitable for development against other zoonotic influenza viruses.

Circulation, Evolution and Transmission of H5N8 virus, 2016-2018.

OBJECTIVES: A second wave of highly pathogenic avian influenza A virus (HPAIV) H5N8 clade 2.3.4.4 has spread globally, causing outbreaks among wild birds and domestic poultry since autumn 2016. The circulation and evolutionary dynamics of the virus remain largely unknown. METHODS: We performed surveillance for H5N8 in Qinghai Lake in China since the emergence of the virus (from 2016 to 2018). By analyzing recovered viruses in Qinghai Lake and all related viruses worldwide (449 strains), we identified the genotypes, estimated their genesis and reassortment, and evaluated their global distribution and transmission. RESULTS: Through surveillance of wild migratory birds around Qinghai Lake between 2016 and 2018, we revealed that the H5N8 was introduced into Qinghai Lake bird populations (QH-H5N8), with distinct gene constellations in 2016 and 2017. A global analysis of QH-H5N8-related viruses showed that avian influenza viruses with low pathogenicity in wild birds contributed to the high diversity of genotypes; the major reassortment events possibly occurred during the 2016 breeding season and the following winters. CONCLUSIONS: Continued circulation of QH-H5N8-related viruses among wild birds has resulted in the global distribution of high genotypic diversity. Thus, these viruses pose an ongoing threat to wild and domestic bird populations and warrant continuous surveillance.