Low 2018/19 vaccine effectiveness against influenza A(H3N2) among 15–64-year-olds in Europe: exploration by birth cohort

Abstract

Introduction: Influenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE). Aim: The I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort. Methods: We measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0-14, 15-64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32-54-year-olds (1964-86) sharing potential childhood imprinting to serine at haemagglutinin position 159. Results: Influenza A(H3N2) VE among all ages was −1% (95% confidence interval (CI): −24 to 18) and 46% (95% CI: 8-68), −26% (95% CI: −66 to 4) and 20% (95% CI: −20 to 46) among 0-14, 15-64 and ≥ 65-year-olds, respectively. Among 15-64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: −34 to 50) and −74% (95% CI: −259 to 16), respectively. VE was −18% (95% CI: −140 to 41), −53% (95% CI: −131 to −2) and −12% (95% CI: −74 to 28) among 15-31-year-olds (1987-2003), 32-54-yearolds (1964-86) and 55-64-year-olds (1954-63), respectively. Discussion: The lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964-86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15-64-year-olds and the public health impact of the I-REV hypothesis warrant further study.

Predominance of a Drifted Influenza A (H3N2) Clade and Its Association with Age-Specific Influenza Vaccine Effectiveness Variations, Influenza Season 2018–2019

“…The low all-ages influenza A (H3N2) VE estimate observed in Israel, was consistent with the genetic and antigenic analysis of these viruses. In addition, it was consistent with the all-ages influenza A (H3N2) clade 3C.3a VE estimates in the USA [21], Canada [20], and Europe [22].…”

“…Recent studies by Skowronski et al [20] and Kissling et al [22] demonstrated statistically significant negative 2018-2019 influenza A (H3N2) VE estimates among the age ranges of 39-53 years old [20] and 32-54 years old [22], respectively. Skowronski et al hypothesized that immune imprinting that occurred during childhood towards a common epitope of the hemagglutinin (HA) protected adults that did not receive the 2018-2019 influenza vaccine against the circulating 3C.3a influenza A (H3N2) viruses, whereas the immune response elicited by the 2018-2019 mismatched influenza A (H3N2) vaccine antigen interfered with this protection [20].…”

“…Estimation of VE for predetermined age groups is valuable; however, given the distinct character of such groups, it may not provide enough information regarding the trend of VE at various ages. Using the 15 year moving interval allowed us to evaluate VE at various ages despite the fact that our sample size may be smaller than that of larger countries [8,22,23]. This approach demonstrated the transition from negative to positive influenza A (H3N2) VE point estimates with age ( Figure 4A,B).…”

Interim estimates of 2019/20 vaccine effectiveness during early-season co-circulation of influenza A and B viruses, Canada, February 2020

“…An immunological cohort effect (i.e. imprint-regulated effect of vaccine; I-ReV) was hypothesised last season to explain the paradoxical negative VE for the 3C.2a1 vaccine against 3C.3a viruses, notably among adults 35-54 years of age [25,28,29]. Whether the I-ReV hypothesis may also apply, but in reverse, to explain this season's protective VE for 3C.3a vaccine against 3C.2a1 viruses requires greater sample size to explore.…”

Influenza Vaccination in Italian Healthcare Workers (2018–2019 Season): Strengths and Weaknesses. Results of a Cohort Study in Two Large Italian Hospitals

“…Studies conducted by other authors have found moderate IVE in the 2018-2019 season [3,[38][39][40]. It must be pointed out, however, that the design of all the published studies was different from ours; indeed, they were case-control test-negative studies in primary care and hospital settings.…”