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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

1
British Columbia Centre for Disease Control, Vancouver.
2
University of British Columbia, Vancouver.
3
Institut National de Santé Publique du Québec.
4
Laval University, Québec.
5
Centre Hospitalier Universitaire de Québec, Québec.
6
Public Health Ontario, Toronto.
7
University of Calgary, Calgary.
8
University of Toronto, Toronto.
9
Alberta Provincial Laboratory, Edmonton.
10
University of Alberta, Edmonton.
11
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.

Abstract

Background:

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.

Methods:

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.

Results:

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).

Conclusions:

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.

KEYWORDS:

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

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