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Early estimates of seasonal influenza vaccine effectiveness against influenza requiring medical attention at primary care level in Europe, week 41 - 49, 2025

Epidemiological update

The 2025/26 influenza season has begun earlier than the previous two seasons, driven by the recently-emerged influenza virus A(H3N2) subclade K. There have been concerns over the effectiveness of seasonal influenza vaccines this season due to the mismatch between the vaccine and the new subclade.

Preliminary data from the Vaccine Effectiveness, Burden and Impact Studies (VEBIS) primary care multicentre study indicate that the seasonal vaccines available in EU are providing protection against influenza A(H3N2) infection, with vaccine effectiveness ranging from 52% to 57%. These preliminary early estimates support current efforts to offer seasonal influenza vaccination to key populations in the shortest time possible, to mitigate the impact of influenza infections, which is expected to be substantial in the the currnt season. 

In the context of increasing circulation of influenza, especially A(H3N2), ECDC has provided comprehensive advice on vaccination, the use of antivirals, the use of face masks in healthcare and long-term care facilities, and healthcare preparedness in the Threat Assessment Brief: Assessing the risk of influenza for the EU/EEA in the context of increasing circulation of A(H3N2) subclade K. 

Epidemiological situation

High circulation of influenza viruses

In 2025, influenza activity across the EU/EEA increased three to four weeks earlier than in the previous two seasons. 

As of week 49, 2025, there is significant respiratory virus circulation in the European Union/European Economic Area (EU/EEA) as the number of patients presenting to primary care with symptoms of respiratory illness is elevated in approximately half of reporting countries. Most countries now report widespread activity at low-to-medium intensity, while the influenza virus circulation continues to increase.

Influenza A is dominant in all countries, with A(H3N2) subclade K driving the increasing trend in recent weeks. Circulation is highest in children aged 5–14 years. Increases in hospitalisation are being observed in some countries, affecting all age groups, but primarily adults aged 65 years and above.

Early estimates of influenza vaccine effectiveness 

ECDC, together with a large consortium of EU/EEA partners, has been implementing multicountry vaccine effectiveness studies for seasonal influenza for many years as part of the Influenza Monitoring of Vaccine Effectivenss (I-MOVE) network within the VEBIS programme. This study recruits patients of all ages presenting with acute respiratory infection (ARI) or influenza-like illness (ILI) to participating primary care physicians in the EU/EEA. The studies are based on a validated methodology which uses a test negative design and which has been extensively described in the EU setting [1-4].

A total of 866 influenza cases and 4 165 test-negative controls were included in the multi-country study across all age groups between week 41 and week 49, 2025. Almost all cases were influenza A (865/866), with only one influenza B case. Among subtyped influenza A viruses (85%; 736/865), 75% (n=553) were influenza A(H3N2), and 25% (n=183) were influenza A(H1N1)pdm09. 

The majority (93%; 807/866) of individuals with influenza who presented for primary care consultation and who met the case definitions were aged <65 years, with more than half (54%; 467/866) being children (<18 years). 

Early seasonal influenza vaccine effectiveness estimates were calculated for the period week 41-49 2025, by influenza subtype and age (when data stratifications allowed). It was not possible to estimate vaccine effectiveness separately for individuals aged 65 years and older, due to the low number of influenza cases included in the study. 

Across the total population (all age groups), vaccine effectiveness was:

  • 44% (95% CI: 25–59) against any influenza;
  • 52% (95% CI: 29–69) against influenza A(H3N2);
  • 16% (95% CI: -43–54) against influenza A(H1N1)pdm09. 

Age-specific vaccine effectiveness estimates for A(H3N2) were 52% (95% CI: 21-72) among those aged 0–17 years and 57% (95% CI: 4-84) among those aged 18–64 years. Due to the dominance of influenza A(H3N2), estimates for other influenza subtypes are imprecise at this time in the season.

In recent weeks, the increase in influenza circulation has been largely driven by influenza A(H3N2) subclade K, which is drifted from the vaccine strain. Data from the VEBIS primary care multicentre study I-MOVE, indicate that the seasonal vaccines available in EU provide protection against influenza A(H3N2) infection. These results are consistent with findings from England [5] and pooled results from Scotland, Wales and Northern Ireland [6].

These preliminary results should be interpreted cautiously. Firstly, the precision of vaccine effectiveness estimates is low at this stage of the season (especially for influenza A(H1N1)pdm09) due to small sample sizes. Secondly, the estimates may change during the season, depending on evolving disaease epidemiology and influenza virus subtype dominance. Thirdly, the current level of protection may decline over time, particularly in a proponged influenza season. Finally, estimates may change as the precision of studies increase with the inclusion of more participants, which will require close monitoring in the coming months.

These early estimates of influenza vaccine effectiveness support current efforts to offer seasonal influenza vaccination to key populations in the shortest time possible. Comprehensive ECDC advice to mitigate the impact of seasonal influenza in the context of increasing circulation of A(H3N2) subclade K, can be found here: Threat Assessment Brief: Assessing the risk of influenza for the EU/EEA in the context of increasing circulation of A(H3N2) subclade K

Methods

Since the end of 2020, ECDC has contracted Epiconcept and a consortium of partners under the VEBIS framework contract. One of these studies, I-MOVE, investigates seasonal influenza and COVID-19 vaccine effectiveness against laboratory confirmed ILI in primary care settings across participating EU/EEA countries and sites [7-8]. 

Data included in this Epidemiological Update were from participating sites in France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain (Navarra), Spain (National), and Romania. Data from other participating countries/sites were not included due to too few influenza cases (<5) during the period reported (week 41 to week 49, 2025). 

Of note, early influenza vaccine effectiveness estimates are based on low sample size and should be interpreted with caution. The precision around these estimates is low at this stage of the influenza season. The estimates may change as the influenza season progresses and more participants are recruited into the study.

The study design is a test negative case control study. All patients presenting who met the European Union case definition for ARI or ILI, are swabbed within eight days of symptom onset, and tested for influenza virus using real-time reverse-transcription polymerase chain reaction (PCR). Confirmed influenza cases are patients who tested positive for influenza, while controls are patients who tested negative. Individuals with influenza who also tested PCR-positive for SARS-CoV-2 and/or respiratory syncytial virus (RSV) were excluded. A patient was defined as vaccinated if they had received a 2025 influenza vaccine 14 or more days before symptom onset.

For each study site, only patients presenting with symptoms 14 or more days after the start of the national or regional 2025 influenza vaccination campaign are included. Influenza A cases that were not further subtyped were excluded from the influenza A(H1N1)pdm09 and A(H3N2) vaccine effectiveness analyses. 

A logistic regression model was used to calculate vaccine effectiveness including a priori confounding factors: age, date of symptom onset, sex, and presence of at least one chronic condition.

The same study design and methods, including statistical analysis, have been used to calculate influenza vaccine effectiveness in previous seasons. Results from previous seasons have been published in peer-reviewed journals [3-6].

Further details on the study design and methods, participating sites, the study protocol, and list of peer-reviewed publications are available on the ECDC website: Vaccine Effectiveness, Burden and Impact Studies (VEBIS)

Acknowledgements

ECDC acknowledges the country experts and the VEBIS consortium and network who have been implementing the study.

References

  1. Kissling E, Maurel M, Pozo F, Pérez-Gimeno G, Buda S, Sève N et al. Influenza vaccine effectiveness in Europe and the birth cohort effect against influenza A(H1N1)pdm09: VEBIS primary care multicentre study, 2023/24. Euro Surveill. 2025;30(23):pii=2500011. https://doi.org/10.2807/1560-7917.ES.2025.30.23.2500011
  2. Marine Ml, Clara M, Luise G, Beatrix O, Mariette H, Ausenda M et al. Exploring the effect of clinical case definitions on influenza vaccine effectiveness estimation at primary care level: Results from the end-of-season 2022–23 VEBIS multicentre study in Europe, Vaccine, Volume 42, Issue 16, 2024, Pages 3547-3554, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2024.04.060.
  3. Maurel M, Howard J, Kissling E, Pozo F, Pérez-Gimeno G, Buda S et al. Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024. Euro Surveill. 2024;29(8):pii=2400089. https://doi.org/10.2807/1560-7917.ES.2024.29.8.2400089
  4. Maurel M, Pozo F, Pérez-Gimeno G, Buda S, Sève N, Oroszi B et al. Influenza vaccine effectiveness in Europe: Results from the 2022–2023 VEBIS (Vaccine Effectiveness, Burden and Impact Studies) primary care multicentre study. Influenza Other Respi Viruses. 2024; 18(1):e13243. doi:10.1111/irv.13243
  5. Kirsebom FCM, Thompson C, Talts T, Kele Bx, Whitaker H J, Andrews N, et al. Early influenza virus characterisation and vaccine effectiveness in England in autumn 2025, a period dominated by influenza A(H3N2) subclade K. Euro Surveill. 2025;30(46):pii=2500854. https://doi.org/10.2807/1560-7917.ES.2025.30.46.2500854.
  6. Health and Social Care (HSC) Public Health Agency, Respiratory surveillance report – Northern Ireland - Week 49: 01 December 2025 – 07 December 2025. Available from: Respiratory surveillance report | HSC Public Health Agency
  7. European Centre for Disease Prevention and Control (ECDC). Vaccine Effectiveness, Burden and Impact Studies (VEBIS) [Internet]. Stockholm: ECDC; [cited 2025 Jan 19]. Available from: https://www.ecdc.europa.eu/en/infectious-disease-topics/related-public-health-topics/immunisation-and-vaccines/vebis
  8. European Centre for Disease Prevention and Control (ECDC). Vaccine effectiveness: VEBIS Lot 5 sites, September 2024 [Internet]. Stockholm: ECDC; 2024 [cited 2025 Jan 19]. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/vaccine-effectiveness-vebis-lot-5-sites-september-2024_EK.pptx 

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