Abstract
While the early start and higher intensity of the 2012/13 influenza A virus (IAV) epidemic was not unprecedented, it was the first IAV epidemic season since the 2009 H1N1 influenza pandemic where the H3N2 subtype predominated. We directly sequenced the genomes of 154 H3N2 clinical specimens collected throughout the epidemic to better understand the evolution of H3N2 strains and to inform the H3N2 vaccine selection process. Phylogenetic analyses indicated that multiple co-circulating clades and continual antigenic drift in the haemagglutinin (HA) of clades 5, 3A, and 3C, with the evolution of a new 3C subgroup (3C-2012/13), were the driving causes of the epidemic. Drift variants contained HA substitutions and alterations in the potential N-linked glycosylation sites of HA. Antigenic analysis demonstrated that viruses in the emerging subclade 3C.3 and subgroup 3C-2012/13 were not well inhibited by antisera generated against the 3C.1 vaccine strains used for the 2012/13 (A/Victoria/361/2011) or 2013/14 (A/Texas/50/2012) seasons. Our data support updating the H3N2 vaccine strain to a clade 3C.2 or 3C.3-like strain or a subclade that has drifted further. They also underscore the challenges in vaccine strain selection, particularly regarding HA and neuraminidase substitutions derived during laboratory passage that may alter antigenic testing accuracy.
Highlights
Influenza viruses cause significant annual morbidity and mortality in the global human population [1]
Phylogenetic analyses of HA nucleotide sequences showed that the majority of circulating H3N2 strains arose from three major H3 clades: 5, 3A, and 3C (Figure 1A; clade nomenclature was adopted from United States (US) Centers for Disease Control and Prevention (CDC) [25])
The backbone of the phylogeny had a ladder-like structure with relatively short terminal branches indicative of seasonal influenza A virus (IAV) antigenic drift arising from immune escape
Summary
Influenza viruses cause significant annual morbidity and mortality in the global human population [1]. The error-prone IAV RNA polymerase frequently generates nucleotide substitutions that can lead to a selective advantage in all eight genomic viral RNA segments (vRNAs), new epidemic variants are most frequently due to accumulated substitutions in the two surface glycoproteins, haemagglutinin (HA) and neuraminidase (NA). Antigenic drift necessitates frequent updating of the strains used in the influenza vaccine [3,4]. This requires global surveillance of the antigenic profile of circulating strains to inform the decisions made at biannual World Health Organization (WHO) meetings for the selection of influenza vaccine strains [4,5,6]. The acquisition of as few as one to five mutations in HA can necessitate an updated vaccine strain to optimally protect the public [7,8]
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