title: A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low Influenza Vaccine Effectiveness During the 2014-2015 Season.
abstract: The 2014-2015 influenza season was distinguished by an epidemic of antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013-2014. We report 2014-2015 vaccine effectiveness (VE) from Canada and explore contributing agent-host factors.
  
  
  
  VE against laboratory-confirmed influenza was derived using a test-negative design among outpatients with influenza-like illness. Sequencing identified amino acid mutations at key antigenic sites of the viral hemagglutinin protein.
  
  
  
  Overall, 815/1930 (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%) influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577; 99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460 (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations F159Y (a cluster-transition position) and K160T (a predicted gain of glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2) was -17% (95% confidence interval [CI], -50% to 9%) overall with clade-specific VE of -13% (95% CI, -51% to 15%) for clade 3C.2a but 52% (95% CI, -17% to 80%) for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients vaccinated in 2014-2015 only, significantly lower at -32% (95% CI, -75% to 0%) if also vaccinated in 2013-2014 and -54% (95% CI, -108% to -14%) if vaccinated each year since 2012-2013. VE against clade-mismatched B(Yamagata) viruses was 42% (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination compared to A(H3N2).
  
  
  
  Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014-2015.
authors.affiliation: British Columbia Centre for Disease Control.|University of British Columbia, Vancouver.
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Skowronski
authors.affiliation: British Columbia Centre for Disease Control.
authors.forename: Catharine
authors.initials: C
authors.lastname: Chambers
authors.affiliation: British Columbia Centre for Disease Control.
authors.forename: Suzana
authors.initials: S
authors.lastname: Sabaiduc
authors.affiliation: Institut National de Santé Publique du Québec.|Laval University.|Centre Hospitalier Universitaire de Québec.
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.affiliation: Public Health Ontario, Toronto.
authors.forename: Anne-Luise
authors.initials: AL
authors.lastname: Winter
authors.affiliation: University of Calgary.
authors.forename: James A
authors.initials: JA
authors.lastname: Dickinson
authors.affiliation: British Columbia Centre for Disease Control.|University of British Columbia, Vancouver.
authors.forename: Mel
authors.initials: M
authors.lastname: Krajden
authors.affiliation: Public Health Ontario, Toronto.|University of Toronto.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Gubbay
authors.affiliation: University of Alberta.|Alberta Provincial Laboratory, Edmonton.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Drews
authors.affiliation: Institut National de Santé Publique du Québec.
authors.forename: Christine
authors.initials: C
authors.lastname: Martineau
authors.affiliation: Public Health Ontario, Toronto.
authors.forename: Alireza
authors.initials: A
authors.lastname: Eshaghi
authors.affiliation: British Columbia Centre for Disease Control.
authors.forename: Trijntje L
authors.initials: TL
authors.lastname: Kwindt
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bastien
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D016679:Genome, Viral / Q000235:genetics*; D006801:Humans; D007223:Infant; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008297:Male; D008875:Middle Aged; D018571:Sentinel Surveillance; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines
keywords: antigenic drift; genomics; influenza vaccines; sentinel surveillance; vaccine effectiveness