Progressive antigenic drift and phylogeny of human influenza A(H3N2) virus over five consecutive seasons (2009–2013) in Hangzhou, China

• We find progressive antigenic drift of human influenza A(H3N2) virus in Hangzhou.
• The correspondent epitopes of the circulating viruses shifted from C-D-E to A-B.
• HA and NA underwent independent evolutionary pathways during the recent seasons.
• Our findings underscore a possibly early warning for variants with antigen

SummaryVaccine efficacy (VE) can be affected by progressive antigenic drift or any new reassortment of influenza viruses. To effectively track the evolution of human influenza A(H3N2) virus circulating in Hangzhou, China, a total of 65 clinical specimens were selected randomly from outpatients infected by A(H3N2) viruses during the study period from November 2009 to December 2013. The results of reduced VE and antigenic drift of the correspondent epitopes (C–D–E to A–B) suggest that the current vaccine provides suboptimal protection against the A(H3N2) strains circulating recently. Phylogenetic analysis of the entire HA and NA sequences demonstrated that these two genes underwent independent evolutionary pathways during recent seasons. The H3-based phylogenetic tree showed that a special strain A/Hangzhou/A289/2012 fell in a cluster among viruses with reduced VE predominantly circulating in 2013. Our findings underscore a possible early warning for the circulation of A(H3N2) variants with antigenic drift during the previous seasons.