title: Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses.
abstract: 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.
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sandbulte
authors.forename: Kim B
authors.initials: KB
authors.lastname: Westgeest
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
authors.forename: Colin A
authors.initials: CA
authors.lastname: Russell
authors.forename: David F
authors.initials: DF
authors.lastname: Burke
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Smith
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Maryna C
authors.initials: MC
authors.lastname: Eichelberger
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry*; D019143:Evolution, Molecular; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry*; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry*; D007252:Influenza Vaccines / Q000737:chemistry; D007251:Influenza, Human / Q000517:prevention & control / Q000821:virology; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D009439:Neuraminidase / Q000737:chemistry*; D016865:Reassortant Viruses / Q000737:chemistry
chemical_list: D000941:Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009439:Neuraminidase