title: Genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial.
abstract: Estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. This study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (HA) gene-encoded HA1 domain is a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza virus vaccine efficacy trial involving >43,000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380 viruses), A(H1N1) (29 viruses), B(Yamagata) (23 viruses), and B(Victoria) (66 viruses) from 603 PCR- or culture-confirmed specimens. Unlike the B strains, most A(H3N2) (377 viruses) and all A(H1N1) viruses were classified as homologous to the respective vaccine strains based on their HA1 domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48% (182/380) of A(H3N2) and 86% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses classified as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR is a sensitive diagnostic method for confirming influenza virus cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity; hence, it may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine strain for estimating vaccine efficacy in a prospective clinical trial.
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Serge
authors.initials: S
authors.lastname: Durviaux
authors.forename: John
authors.initials: J
authors.lastname: Treanor
authors.forename: Jiri
authors.initials: J
authors.lastname: Beran
authors.forename: Xavier
authors.initials: X
authors.lastname: Duval
authors.forename: Meral
authors.initials: M
authors.lastname: Esen
authors.forename: Gregory
authors.initials: G
authors.lastname: Feldman
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Janet E
authors.initials: JE
authors.lastname: McElhaney
authors.forename: Andrzej
authors.initials: A
authors.lastname: Nowakowski
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Ruiz-Palacios
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: van Essen
authors.forename: Lidia
authors.initials: L
authors.lastname: Oostvogels
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Devaster
authors.forename: Karl
authors.initials: K
authors.lastname: Walravens
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D002986:Clinical Trials as Topic; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology*; D008297:Male; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D050505:Mutant Proteins