Impact of naturally occurring #hemagglutinin substitutions on antigenicity and fitness of #influenza #H5N1 virus
Abstract In 2024, a human infection with clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) virus was identified in the United States in an individual with no known exposure . Genetic analysis revealed two hemagglutinin (HA) substitutions, P136S and A156T, which may alter viral antigenicity . Virus isolation was unsuccessful, preventing timely serologic analysis. To overcome this limitation, we generated recombinant viruses by reverse genetics and characterized the effects of the substitutions on antigenicity, receptor binding , and replicative fitness. The A156T substitution introduced a potential N-linked glycosylation site , resulting in altered antigenicity and reduced replication in primary human nasal epithelial cells and ferrets . Importantly, the A(H5N1) candidate vaccine virus (CVV) IDCDC-RG80A, which possesses HA-T156, remained antigenically effective against viruses with and without these substitutions. These findings highlight the importance of sequencing, rever...