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.

<b>研究目的</b>：研究者针对2016-2017季检出的A型流感病毒H3N2亚型的血凝素（hemagglutinin, HA）基因开展了深入的系统发育分析，旨在将流行毒株与卵源及细胞源2016-2017候选疫苗病毒（candidate vaccine virus, CVV）进行比对。<b>研究方法</b>：本研究对2016-2017季检出的162条H3N2病毒HA1区域序列进行系统发育分析，并与卵源/细胞源候选疫苗病毒进行比对。采用表位模型（P_epitope）量化评估卵源、细胞源候选疫苗病毒针对野外分离毒株的预测疫苗效力（predicted vaccine efficacy, pVE）。<b>研究结果</b>：所有H3N2毒株均隶属于3C.2a遗传进化支，其中80.2%的毒株属于3C.2a1亚进化支。2016-2017季流行的H3N2病毒存在多种变异株。野外分离的H3N2毒株的HA序列与细胞源候选疫苗病毒的同源性显著高于卵源候选疫苗病毒。卵源候选疫苗病毒中160位与194位氨基酸发生的替换突变，对预测疫苗效力产生影响，卵源候选疫苗病毒的预测疫苗效力低于细胞源候选疫苗病毒。<b>研究结论</b>：本研究结果表明，2016-2017季观测到的疫苗保护效力下降，可能源于疫苗毒株在卵适应培养过程中HA基因发生的突变——而卵培养是当前全球多数流感疫苗生产体系的核心基础。因此，采用无卵源疫苗生产体系有助于提升流感疫苗的保护效果。