Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

MR Sandbulte, Kim Westgeest, JA Gao, XY Xu, AI Klimov, CA Russell, DF Burke, Derek Smith, Ron Fouchier, MC Eichelberger

Research output: Contribution to journalArticleAcademicpeer-review

144 Citations (Scopus)


Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.
Original languageEnglish
Pages (from-to)20748-20753
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of Ame
Issue number51
Publication statusPublished - 2011


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