A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low Influenza Vaccine Effectiveness During the 2014-2015 Season

Clin Infect Dis. 2016 Jul 1;63(1):21-32. doi: 10.1093/cid/ciw176. Epub 2016 Mar 29.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014-2015.

Keywords: antigenic drift; genomics; influenza vaccines; sentinel surveillance; vaccine effectiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Canada / epidemiology
  • Child
  • Child, Preschool
  • Female
  • Genome, Viral / genetics*
  • Humans
  • Infant
  • Influenza A virus* / genetics
  • Influenza A virus* / immunology
  • Influenza B virus* / genetics
  • Influenza B virus* / immunology
  • Influenza Vaccines / immunology*
  • Influenza, Human* / epidemiology
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Influenza, Human* / virology
  • Male
  • Middle Aged
  • Sentinel Surveillance
  • Young Adult

Substances

  • Influenza Vaccines