A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses [Vaccines and Antiviral Agents]

IMPORTANCE

The possible avian flu epidemic remains a threat to public health and fitness, because the avian-originated influenza A(H7N9) virus has caused more than 1560 laboratory-confirmed human infections since 2013, with almost 40 percent mortality. However, CVVs in cells and chicken eggs’ growth is often a challenge. These G218E CVVs shielded ferrets from lethal challenge with the virus, and kept the antigenicity determined by hemagglutination inhibition assay. We discovered that the sub-optimal replication of the parental h 7 CVVs was correlated with impeded progeny virus release as a consequence of strong HA receptor binding relative to feeble neuraminidase (NA) cleavage of glands. By comparison, the G218E-mediated growth progress was related to balanced HA and NA functions, resulted from reduced HA to both human- and also thus eased, and avian-type receptors virus release. Our findings revealed a single amino acid mutation at residue 218 of those HA improved the development of A(H7N9) flu virus by balancing HA and NA works, reducing light on an alternative approach for optimizing certain flu CVVs.

The circulating avian influenza A(H7N9) has caused recurrent outbreak waves with high mortality in China since 2013, where the borderline tide crossing 2016 and 2017 was emphasized by high amount of infections and emergence of highly pathogenic avian influenza (HPAI) A(H7N9) breeds in human circumstances. We generated non pathogenic reassortant CVVs produced from the emerging (H7N9) with improved virus replication and protein yield in both MDCK eggs and cells by introducing one substitution, G218E, into HA, that was correlated with reducing HA receptor binding and also balancing HA-NA functions. The in vitro and in vivo experiments demonstrated comparable antigenicity of their G218E CVVs with that of their WT counterparts, and the WT and also G218E CVVs fully protected ferrets from civic HPAI virus battle. With high yield faculties and also the estimated antigenicity, the G218E CVVs has to benefit the pandemic preparedness against the A(H7N9) influenza threat.

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