2025/26 subclade-specific influenza A and B vaccine effectiveness estimates and discordant laboratory-based indicators of vaccine match or mismatch
- 1British Columbia Centre for Disease Control
Abstract
BackgroundThe 2025/26 influenza season included A(H3N2) subclade K predominance with A(H1N1)pdm09 co-circulation and subsequent prolonged influenza B activity. The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) in the context of genetic and antigenic relatedness to circulating viruses.
MethodsWe estimated VE by test-negative design among outpatients with medically-attended acute respiratory illness between November and April. We characterized case viruses by whole genome sequencing and hemagglutination inhibition assay.
ResultsAmong 2809/9047 (31%) influenza-positive specimens, 82% (2306/2809) were influenza A with 18% (504/2809) influenza B. Of subtyped influenza A, 85% (1848/2169) were A(H3N2).
We sequenced 59% (1099/1848) of A(H3N2) viruses, with 87% (956/1099) subclade K, antigenically-mismatched to subclade J.2 vaccine. VE against A(H3N2) and subclade K was 38% (95% confidence interval: 27%-47%) and 33% (19%-45%).
We sequenced 69% (222/323) of A(H1N1)pdm09 viruses, virtually all (n=218) clade 5a.2a.1, including subclades D.3.1 (21%; n=47) and D.3.1.1 (77%; n=171), antigenically-matched to subclade D vaccine. VE against A(H1N1)pdm09, subclades D.3.1 and D.3.1.1 was 28% (4%-47%), -21% (-144%-40%) and 44% (14%-64%).
We sequenced 82% (413/504) of influenza B viruses, all B/Victoria, including antigenically-mismatched subclade C.3 (18%; n=74) with D197N gain-of-glycosylation, and antigenically-matched subclade C.5 (82%; n=339) relative to subclade C vaccine. VE against influenza B, subclades C.3 and C.5 was 55% (41%-66%), 10% (-60%-49%) and 68% (51%-79%).
ConclusionsThe 2025/26 influenza vaccine reduced the risk of A(H3N2), A(H1N1)pdm09 and B/Victoria by over one-third, one-quarter and one-half, respectively. Laboratory-based indicators of vaccine match remain uncertain proxies for actual vaccine protection, reinforcing importance of annual epidemiological monitoring of VE.
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BibTeX
@misc{separovic2026202526,
title = {{2025/26 subclade-specific influenza A and B vaccine effectiveness estimates and discordant laboratory-based indicators of vaccine match or mismatch}},
author = {L. Separovic and S. E. Kaweski and M. B. Cox and Y. Zhan and S. Sabaiduc and R. Olsha and M. Hasso and R. G. Mather and S. Carazo and C. Lacroix and I. Meunier and L. N. Salhi and J. A. Dickinson and N. Zelyas and A. N. Jassem and K. Dover and C. Ranadheera and R. Gao and N. Bastien and D. M. Skowronski},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.26362769},
url = {https://www.medrxiv.org/content/10.64898/2026.09.10.26362769v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - 2025/26 subclade-specific influenza A and B vaccine effectiveness estimates and discordant laboratory-based indicators of vaccine match or mismatch
AU - L. Separovic
AU - S. E. Kaweski
AU - M. B. Cox
AU - Y. Zhan
AU - S. Sabaiduc
AU - R. Olsha
AU - M. Hasso
AU - R. G. Mather
AU - S. Carazo
AU - C. Lacroix
AU - I. Meunier
AU - L. N. Salhi
AU - J. A. Dickinson
AU - N. Zelyas
AU - A. N. Jassem
AU - K. Dover
AU - C. Ranadheera
AU - R. Gao
AU - N. Bastien
AU - D. M. Skowronski
PY - 2026
DA - 2026/09/10
PB - medRxiv
DO - 10.64898/2026.09.10.26362769
UR - https://www.medrxiv.org/content/10.64898/2026.09.10.26362769v1
AB - BackgroundThe 2025/26 influenza season included A(H3N2) subclade K predominance with A(H1N1)pdm09 co-circulation and subsequent prolonged influenza B activity. The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) in the context of genetic and antigenic relatedness to circulating viruses. MethodsWe estimated VE by test-negative design among outpatients with medically-attended acute respiratory illness between November and April. We characterized case viruses by whole genome sequencing and hemagglutination inhibition assay. ResultsAmong 2809/9047 (31%) influenza-positive specimens, 82% (2306/2809) were influenza A with 18% (504/2809) influenza B. Of subtyped influenza A, 85% (1848/2169) were A(H3N2). We sequenced 59% (1099/1848) of A(H3N2) viruses, with 87% (956/1099) subclade K, antigenically-mismatched to subclade J.2 vaccine. VE against A(H3N2) and subclade K was 38% (95% confidence interval: 27%-47%) and 33% (19%-45%). We sequenced 69% (222/323) of A(H1N1)pdm09 viruses, virtually all (n=218) clade 5a.2a.1, including subclades D.3.1 (21%; n=47) and D.3.1.1 (77%; n=171), antigenically-matched to subclade D vaccine. VE against A(H1N1)pdm09, subclades D.3.1 and D.3.1.1 was 28% (4%-47%), -21% (-144%-40%) and 44% (14%-64%). We sequenced 82% (413/504) of influenza B viruses, all B/Victoria, including antigenically-mismatched subclade C.3 (18%; n=74) with D197N gain-of-glycosylation, and antigenically-matched subclade C.5 (82%; n=339) relative to subclade C vaccine. VE against influenza B, subclades C.3 and C.5 was 55% (41%-66%), 10% (-60%-49%) and 68% (51%-79%). ConclusionsThe 2025/26 influenza vaccine reduced the risk of A(H3N2), A(H1N1)pdm09 and B/Victoria by over one-third, one-quarter and one-half, respectively. Laboratory-based indicators of vaccine match remain uncertain proxies for actual vaccine protection, reinforcing importance of annual epidemiological monitoring of VE.
ER -