Send to

Choose Destination
J Infect Dis. 2017 Dec 19;216(12):1487-1500. doi: 10.1093/infdis/jix526.

Beyond Antigenic Match: Possible Agent-Host and Immuno-epidemiological Influences on Influenza Vaccine Effectiveness During the 2015-2016 Season in Canada.

Author information

British Columbia Centre for Disease Control, Vancouver.
University of British Columbia, Vancouver.
Institut National de Santé Publique du Québec.
Laval University, Québec.
Centre Hospitalier Universitaire de Québec, Québec.
Public Health Ontario, Toronto.
University of Calgary, Calgary.
University of Toronto, Toronto.
Alberta Provincial Laboratory, Edmonton.
University of Alberta, Edmonton.
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.



Vaccine effectiveness (VE) estimates for 2015-2016 seasonal influenza vaccine are reported from Canada's Sentinel Practitioner Surveillance Network (SPSN). This season was characterized by a delayed 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) epidemic and concurrent influenza B(Victoria) virus activity. Potential influences on VE beyond antigenic match are explored, including viral genomic variation, birth cohort effects, prior vaccination, and epidemic period.


VE was estimated by a test-negative design comparing the adjusted odds ratio for influenza test positivity among vaccinated compared to unvaccinated participants. Vaccine-virus relatedness was assessed by gene sequencing and hemagglutination inhibition assay.


Analyses included 596 influenza A(H1N1)pdm09 and 305 B(Victoria) cases and 926 test-negative controls. A(H1N1)pdm09 viruses were considered antigenically related to vaccine (unchanged since 2009), despite phylogenetic clustering within emerging clade 6B.1. The adjusted VE against A(H1N1)pdm09 was 43% (95% confidence interval [CI], 25%-57%). Compared to other age groups, VE against A(H1N1)pdm09 was lower for adults born during 1957-1976 (25%; 95% CI, -16%-51%). The VE against A(H1N1)pdm09 was also lower for participants consecutively vaccinated during both the current and prior seasons (41%; 95% CI, 18%-57%) than for those vaccinated during the current season only (75%; 95% CI, 45%-88%), and the VE among participants presenting in March-April 2016 (19%; 95% CI, -15%-44%) was lower than that among those presenting during January-February 2016 (62%; 95% CI, 44%-74%). The adjusted VE for B(Victoria) viruses was 54% (95% CI, 32%-68%), despite lineage-level mismatch to B(Yamagata) vaccine. The further variation in VE as observed for A(H1N1)pdm09 was not observed for B(Victoria).


Influenza VE findings may require consideration of other agent-host and immuno-epidemiologic influences on vaccine performance beyond antigenic match, including viral genomic variation, repeat vaccination, birth (immunological) cohort effects, and potential within-season waning of vaccine protection.


Influenza; birth cohort effects; hemagglutination inhibition; influenza A subtype; influenza B lineage; influenza vaccine; original antigenic sin; repeat vaccination; sequencing; vaccine effectiveness

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center