Influenza Vaccine Effectiveness by A(H3N2) Phylogenetic Subcluster and Prior Vaccination History: 2016-2017 and 2017-2018 Epidemics in Canada

Abstract

Background: The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015-2016 to 3C.2a for 2016-2017 and 2017-2018. Circulating 3C.2a viruses showed considerable hemagglutinin glycoprotein diversification and the egg-adapted vaccine also bore mutations.

Methods: Vaccine effectiveness (VE) in 2016-2017 and 2017-2018 was assessed by test-negative design, explored by A(H3N2) phylogenetic subcluster and prior season's vaccination history.

Results: In 2016-2017, A(H3N2) VE was 36% (95% confidence interval [CI], 18%-50%), comparable with (43%; 95% CI, 24%-58%) or without (33%; 95% CI, -21% to 62%) prior season's vaccination. In 2017-2018, VE was 14% (95% CI, -8% to 31%), lower with (9%; 95% CI, -18% to 30%) versus without (45%; 95% CI, -7% to 71%) prior season's vaccination. In 2016-2017, VE against predominant clade 3C.2a1 viruses was 33% (95% CI, 11%-50%): 18% (95% CI, -40% to 52%) for 3C.2a1a defined by a pivotal T135K loss of glycosylation; 60% (95% CI, 19%-81%) for 3C.2a1b (without T135K); and 31% (95% CI, 2%-51%) for other 3C.2a1 variants (with/without T135K). VE against 3C.2a2 viruses was 45% (95% CI, 2%-70%) in 2016-2017 but 15% (95% CI, -7% to 33%) in 2017-2018 when 3C.2a2 predominated. VE against 3C.2a1b in 2017-2018 was 37% (95% CI, -57% to 75%), lower at 12% (95% CI, -129% to 67%) for a new 3C.2a1b subcluster (n = 28) also bearing T135K.

Conclusions: Exploring VE by phylogenetic subcluster and prior vaccination history reveals informative heterogeneity. Pivotal mutations affecting glycosylation sites, and repeat vaccination using unchanged antigen, may reduce VE.

Keywords: A(H3N2); genomics; influenza vaccine; influenza virus; subtype; vaccine effectiveness.

Figure 1.

Influenza A(H3N2) virus detection by genetic grouping and week of specimen collection, 2016–2017 and 2017–2018 seasons. Among eligible patients presenting with influenza-like illness, influenza A(H3N2) detections overall each season (A) and by phylogenetic subcluster (B) are displayed by week of specimen collection. The overall contribution by phylogenetic subcluster is shown in pie charts by season. Case counts by subcluster are shown in the legend by season as (n = 2016–2017, n 2017–2018).

Figure 2.

Influenza VE estimates against influenza A(H3N2), 2016–2017 and 2017–2018 seasons, are displayed overall and for select phylogenetic subclusters. Additional A(H3N2) VE findings overall are provided in Table 3 and by phylogenetic subcluster in Supplementary Table 11. All estimates were adjusted for age group (1–8, 9–19, 20–49, 50–64, ≥65 years), province (Alberta, British Columbia, Ontario, Quebec), specimen collection interval (≤4 days, 5–7 days), and calendar time (week of specimen collection modeled using natural cubic spline function with 3 equally spaced knots). All estimates displayed were additionally assessed using Firth’s penalized logistic regression [30–32], but remained within 1% (absolute) in 2016–2017 and within 3% (absolute) in 2017–2018. Abbreviations: +, means with the specified substitution; −, means without the specified substitution; CI, confidence interval; NE, not estimated; VE, vaccine effectiveness.

Figure 3.

Influenza vaccine effectiveness (VE) against influenza A(H3N2) by current and/or prior season’s influenza vaccine receipt, 2016–2017 and 2017–2018 seasons. Restricted to participants ≥9 years old and with complete data for current and prior season’s vaccine receipt. The prior and current seasons’ recommended vaccine strains are specified by season, alongside the dominant circulating influenza A(H3N2) clade. Note that the 2015–2016 3C.3a vaccine (cell or egg passaged) is antigenically distinct from the 2016–2017 3C.2a vaccine (cell or egg passaged); the 2016–2017/2017–2018 egg-adapted 3C.2a vaccine is antigenically distinct from 3C.2a2 viruses that predominated in 2017–2018. All estimates were adjusted for age group (9–19, 20–49, 50–64, ≥65 years), province (Alberta, British Columbia, Ontario, Quebec), specimen collection interval (≤4 days; 5–7 days), and calendar time (week of specimen collection modeled using natural cubic spline function with 3 equally spaced knots). All estimates displayed were additionally assessed using Firth’s penalized logistic regression [30–32], but were identical except for current season only vaccination (within 1% absolute in 2016–2017 and within 2% absolute in 2017–2018). Additional details are provided in Supplementary Table 10.