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. 2019 Nov;24(46):1900585.
doi: 10.2807/1560-7917.ES.2019.24.46.1900585.

Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV)

Danuta M Skowronski  1   2 , Suzana Sabaiduc  1 , Siobhan Leir  1 , Caren Rose  1   2 , Macy Zou  1 , Michelle Murti  3   4 , James A Dickinson  5 , Romy Olsha  3 , Jonathan B Gubbay  3   4 , Matthew A Croxen  6   7 , Hugues Charest  8 , Nathalie Bastien  9 , Yan Li  9 , Agatha Jassem  1   2 , Mel Krajden  1   2 , Gaston De Serres  10   11   8
Affiliations

Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV)

Danuta M Skowronski et al. Euro Surveill. 2019 Nov.

Abstract

IntroductionThe Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.AimTo explain a paradoxical signal of increased clade 3C.3a risk among 35-54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.MethodsWe assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.ResultsInfluenza A(H3N2) VE was 17% (95% CI: -13 to 39) overall: 27% (95% CI: -7 to 50) for 3C.2a1b and -32% (95% CI: -119 to 21) for 3C.3a. Among 20-64-year-olds, VE was -7% (95% CI: -56 to 26): 6% (95% CI: -49 to 41) for 3C.2a1b and -96% (95% CI: -277 to -2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35-54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.DiscussionImprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.

Keywords: A(H3N2); Influenza; clade; cohort effect; imprinting; vaccine effectiveness.

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Conflict of interest statement

Conflict of interest: DMS is Principal Investigator on grants received from the Public Health Agency of Canada in support of this work. GDS has received grants for investigator-initiated studies unrelated to influenza vaccine from Pfizer and provided paid expert testimony for the Ontario Nurses Association, the Quebec Ministry of Justice and GSK. MK has received research grants from Roche, Siemens and Hologic for unrelated studies. Other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Vaccine effectiveness against influenza A(H3N2) viruses overall and by age and genetic subgroup, Canadian Sentinel Practitioner Surveillance Network, 2018/19 (n = 1,993)
Figure 2
Figure 2
Percentage histogram of influenza A(H3N2) cases (overall and clade-specific) and controls by single year of age and vaccination status, Canadian Sentinel Practitioner Surveillance Network, 2018/19 (n = 1,993)
Figure 3
Figure 3
Percentage of worldwide influenza A(H3N2) viruses with specified amino acid residues at haemagglutinin (H3) positions 159 and 193, by year, GISAID, 1968–2019 (n = 83,026)
Figure 4
Figure 4
Overall and clade-specific vaccine effectiveness against influenza A(H3N2), explored by age modelled by single year, Canadian Sentinel Practitioner Surveillance Network, 2018/19 (n = 1,735)
See this image and copyright information in PMC

References

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