Background: Vaccine effectiveness (VE) estimates are reported from Canada´s Sentinel Practitioner Surveillance Network (SPSN) for the 2015-16 influenza season, characterized by a delayed A(H1N1)pdm09 epidemic and concurrent B(Victoria) activity. Potential influences beyond antigenic match are explored including viral genomic variation, birth cohort effects, prior vaccination and epidemic period.

Methods: VE was estimated by test-negative design comparing adjusted-odds ratio for influenza test-positivity among vaccinated vs. 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 compared to 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. Adjusted-VE for A(H1N1)pdm09 was 43%(95%CI=25-57%), lower in adults born 1957-1976 (25%;95%CI=-16-51%); in those consecutively vaccinated both current and prior season (41%;95%CI=18-57%) vs. current season only (75%;95%CI=45-88%); and among participants presenting in March-April (19%;95%CI=-15-44%) vs. January-February 2016 (62%;95%CI=44-75%). VE for B(Victoria) viruses was 54%(95%CI=32-68%) despite lineage-level mismatch to B(Yamagata) vaccine and without further variation as observed for A(H1N1)pdm09.

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, birth (immunological) cohort and repeat vaccination effects, and potential within-season waning of vaccine protection.