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. 2025 Dec;14(1):2562045.
doi: 10.1080/22221751.2025.2562045. Epub 2025 Oct 11.

Influenza vaccine effectiveness and genetic diversity: insights from end-of-season community surveillance, France, 2024-2025

Allan De Clercq  1 , François Blanquart  2 , Vincent Vieillefond  3 , Benoit Visseaux  4 , Claire Nour Abou Chakra  5 , Marta C Nunes  5   6 , Alexandra Jacques  7 , Stéphanie Haim-Boukobza  8 , Valentin Wehrle  9 , Guillaume Deleglise  10 , Thomas Duret  10 , Sibylle Bernard-Stoecklin  11 , Danielle Perez Bercoff  12 , Bruno Lina  1   13 , Marie Anne Rameix-Welti  12   14 , Laurence Josset  1   13 , Vincent Enouf  12 , Antonin Bal  1   13 ; RELAB study group
Affiliations

Influenza vaccine effectiveness and genetic diversity: insights from end-of-season community surveillance, France, 2024-2025

Allan De Clercq et al. Emerg Microbes Infect. 2025 Dec.

Abstract

Influenza 2024-2025 season in France was characterized by prolonged duration, unusual co-circulation of all three viruses (A(H1N1)pdm09, A(H3N2), B/Victoria) with several subclades, and substantial healthcare impact. We aimed to investigate the impact of influenza genetic diversity on vaccine effectiveness (VE). A test-negative design study was conducted to estimate VE in a large cohort from the RELAB network of community-based laboratories (n = 77,704 patients). A subset of sequenced samples (n = 2,119 patients) allowed VE estimation for several clades and subclades as well as comparison of subclade distribution by vaccination status. Vaccine coverage was 45% in patients aged 65 years and older (65+). VE based on PCR-confirmed infections was 44% (95% CI: 41-48%) and lower in 65+ individuals, at 25% (95% CI:18-31%) especially for type A virus (23%; 95% CI: 13-32%) compared to type B virus (57%; 95% CI: 35-72%). Sequencing-confirmed VE among individuals vaccinated 15 days to 3 months prior testing, was 41% (95% CI: 14-60%) for A(H1N1)pdm09 and 47% (95% CI: 21-64%) for its main subclade 5a.2a(C.1.9.3); A(H3N2) estimate was 30% (95% CI:5-48%) and 31% (95% CI:4-50%) for 2a.3a.1(J.2) sublclade. The emerging A(H1N1)pdm09 5a.2a.1 (D.3.1) subclade was significantly more frequent among vaccinated individuals compared to unvaccinated. The low vaccine coverage combined with the notably low effectiveness against A(H3N2) and for type A in elderly may have contributed to the high influenza activity this season. The emergence of A(H1N1)pdm09 5a.2a.1 (D.3.1) raises uncertainty and requires surveillance.

Keywords: Influenza; acute respiratory infection; community testing; surveillance; vaccine effectiveness.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Influenza test positivity per week, for non-vaccinated individuals and individuals vaccinated (15 days to 6 months prior testing), (A) Overall activity, (B) Influenza A activity, (C) Influenza B activity, France, October 2024–April 2025 (n = 77,704).
Figure 2.
Figure 2.
Proportion of influenza types by age group: (A) Influenza A activity, (B) Influenza B activity, France, October 2024–April 2025.
Figure 3.
Figure 3.
Dynamics of clades (subclades) of sequenced influenza viruses: (A) Influenza A(H1N1)pdm09 distribution, (B) Influenza A(H1N1)pdm09 proportion, (C) Influenza A(H3N2) distribution, (D) Influenza A(H3N2) proportion, (E) Influenza B/Victoria distribution, (F) Influenza B/Victoria proportion. France, October 2024–June 2025.
Figure 4.
Figure 4.
Vaccine effectiveness against influenza overall, and stratified by virus type and individual characteristics: (A) Evolution of estimates across the season, (B) End-of-season estimates for individuals vaccinated 15 days to 3 months prior to testing, France, October 2024–April 2025 (C) End-of-season estimates for individuals vaccinated 3–6 months prior to testing. France, October 2024–April 2025.
Figure 5.
Figure 5.
Vaccine effectiveness against influenza by virus type, subtype, clade and sub-clade in the study, (A) vaccination status between 15 days and 3 months prior to testing, (B) vaccination status between 3 and 6 months prior to testing, France, October 2024–April 2025.
Figure 6.
Figure 6.
Clade (subclades) frequencies by vaccination status for individuals vaccinated 15 days to 6 months prior to testing, (A) Influenza A(H1N1)pdm09 frequencies, (B) Influenza A(H3N2) frequencies, (C) Influenza B/Victoria frequencies. France, October 2024–June 2025.
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References

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