In-depth phylogenetic analysis of the hemagglutinin gene of influenza A(H3N2) viruses circulating during the 2016-2017 season revealed egg-adaptive mutations of vaccine strains

<b>Objectives</b>: The authors conducted an in-depth phylogenetic analysis of the hemagglutinin (HA) gene of A(H3N2) identified during the 2016–2017 season to compare the circulating strains with both the egg-derived and cell-derived 2016–2017 candidate vaccine virus (CVV). <b>Methods</b>: 162 HA1 sequences of H3N2 viruses identified during the 2016–2017 season were phylogenetically analyzed and compared with egg-/cell-derived CVV. The predicted vaccine efficacy (pVE) of egg-/cell-derived CVV against field strains was quantified by P_epitope model. <b>Results</b>: All H3N2 belonged to 3C.2a genetic clade, most (80.2%) to 3C.2a1 sub-clade. Several H3N2 variants circulated in the 2016–2017 season. HA sequences of field H3N2 strains displayed greater identity with cell-derived CVV than with egg-derived CVV. The amino acid substitutions in positions 160 and 194 identified in egg-derived CVV affected the pVE, which was lower for egg-derived CVV than for cell-derived CVV. <b>Conclusions</b>: The results suggested that reduced vaccine effectiveness observed in 2016–2017 season was probably due to changes in the HA of vaccine strains acquired upon adaptation in eggs, which are the basis of most manufacturing systems currently used globally. Egg-free vaccine manufacturing systems would be advisable to improve the effectiveness of influenza vaccines.