Challenges in antigenic characterization of circulating influenza A(H3N2) viruses during the 2011-2012 influenza season: an ongoing problem?

Abstract

Genetic and antigenic characterization of 37 representative influenza A(H3N2) virus strains isolated in Greece during the 2011-2012 winter season was performed to evaluate matching of the viruses with the seasonal influenza vaccine strain A/Perth/16/2009. Hemagglutinin gene sequence analysis revealed that all Greek strains clustered within the Victoria/208 genetic clade. Furthermore, substitutions in the antigenic and glycosylation sites suggested potential antigenic drift. Our hemagglutination inhibition (HI) analysis showed that the Greek viruses were Perth/16-like; however, these viruses were characterized as Victoria/208-like when tested at the United Kingdom WHO Collaborating Centre (CC) with HI assays performed in the presence of oseltamivir, a finding consistent with the genetic characterization data. Variability in the HI test performance experienced by other European laboratories indicated that antigenic analysis of the A(H3N2) virus has limitations and, until its standardization, national influenza reference laboratories should include genetic characterization results for selection of representative viruses for detailed antigenic analysis by the WHO CCs.

FIG 1

Weekly distribution of the isolation of the 37 influenza A(H3N2) viruses selected for genetic and antigenic characterization. Dashed line (◼), total numbers of clinical specimens positive for A(H3N2) (right vertical axis); solid line (▲), rate of influenza-like illness (ILI) cases in the 2011-2012 influenza season (left vertical axis). Black bars, specimens tested by both the Greek NIC (HPI) and the WHO CC; gray bars, specimens tested by only the Greek NIC. The numbers of viruses tested are shown on each bar.

FIG 2

Evolutionary relationships of Greek influenza A(H3N2) strains (●) with recent European reference and vaccine strains, based on the HA1 domain of the HA protein gene segment. The evolutionary history was inferred using the neighbor-joining method. The percentages of replicate trees in which the associated taxa clustered together in the bootstrap test (1,000 replicates) are shown next to the branches. Only values above 60% are shown. Strains from the 2011-2012 influenza season (◼) and the 2012-2013 influenza season vaccine (◆) are depicted. Reference strains are indicated in bold. A cross symbol () designates a fatal case.