Molecular and antigenic evolution of human influenza A/H3N2 viruses in Quebec, Canada, 2009-2011.

Background: A/H3N2 variability leads to poor vaccine effectiveness when the vaccine strain is not well matched to the circulating virus.

Objectives: We aim to describe the molecular and antigenic evolution of A/H3N2 viruses recovered during the last 3 influenza seasons in Quebec, Canada.

Study Design: Clinical samples from 33 patients with culture-confirmed A/H3N2 infections were collected over 3 consecutive seasons (March 2009-2011). The isolates' HA gene was amplified and sequenced; phylogenetic analyses of the HA1 region were conducted. To characterize A/H3N2 antigenic properties, standard hemagglutination inhibition (HI) and microneutralization (MN) assays were performed.

Results: In 2009, we observed an antigenic drift from A/Brisbane/10/2007 (vaccine strain used in 2008-2009 and 2009-2010) to A/Perth/16/2009 (vaccine strain used in 2010-2011). Antigenic analysis of clinical influenza strains recovered in Quebec during 2009-2010 also illustrated antigenic drift from the previously prevalent A/Brisbane/10/2007-like (March 2009) to A/Perth/16/2009-like (December 2009) strains. In 2010-2011, the emergence of >4 substitutions in 4 different H3 antigenic sites suggested a genetic drift. However, HI and MN results confirmed the emergence of a drift in only 1 strain (8-fold difference in titers), while 19 others remained antigenically similar to A/Perth/16/2009 but exhibited titer differences (2-4-fold) just inferior to the standard definition of a drift.

Conclusion: Antigenic and molecular characterization of H3N2 viruses over three seasons revealed that not only is the number of HA mutations important, but the nature and location of key mutations may play a significant role in antigenic drift.