[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]
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 8,10,11
Affiliations: 1 British Columbia Centre for Disease Control, Vancouver, Canada; 2 University of British Columbia, Vancouver, Canada; 3 Public Health Ontario, Toronto, Canada; 4 University of Toronto, Toronto, Canada; 5 University of Calgary, Calgary, Canada; 6 Alberta Precision Laboratories, Edmonton, Alberta; 7 University of Alberta, Edmonton, Canada; 8 Institut National de Santé Publique du Québec, Québec, Canada; 9 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; 10 Laval University, Quebec, Canada11 Centre Hospitalier Universitaire de Québec, Québec, Canada
Correspondence: Danuta M Skowronski
Citation style for this article: Skowronski Danuta M, Sabaiduc Suzana, Leir Siobhan, Rose Caren, Zou Macy, Murti Michelle, Dickinson James A, Olsha Romy, Gubbay Jonathan B, Croxen Matthew A, Charest Hugues, Bastien Nathalie, Li Yan, Jassem Agatha, Krajden Mel, De Serres Gaston. 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). Euro Surveill. 2019;24(46):pii=1900585. https://doi.org/10.2807/1560-7917.ES.2019.24.46.1900585
Received: 19 Sep 2019; Accepted: 04 Nov 2019
The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.
To 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.
We 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.
Influenza 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.
Imprinting 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.
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Keywords: Seasonal Influenza; Vaccines; H3N2; Origin Antigenic Sin; Canada.