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Multicenter Study
. 2025 Nov 3;23(1):602.
doi: 10.1186/s12916-025-04426-y.

Vaccine effectiveness against influenza A in older adults and the effect of chronic conditions: results from the I-MOVE and VEBIS multicentre European hospital case-control studies, 2015/16-2023/24

Angela Mary Catherine Rose  1 , Nathalie Nicolay  2 , Clara Mazagatos  3 , Iván Martínez-Baz  4 , Odile Launay  5   6 , Laurane De Mot  7 , Antonino Bella  8 , Mihaela Lazar  9 , Ausenda Machado  10 , Monika Kuliešė  11 , Stephen Abela  12 , Vesna Višekruna Vučina  13 , Rianne van Gageldonk-Lafeber  14 , Silvia Bino  15 , Ralf Dürrwald  16 , Iwona Paradowska-Stankiewicz  17 , Judit Krisztina Horváth  18 , Róisín Duffy  19 , Petr Husa  20 , Jim McMenamin  21 , Francisco Pozo  22 , Jennifer Howard  23 , Miriam Latorre-Millán  24 , Jesús Castilla  4 , Liem Binh Luong Nguyen  5 , Nicolas Dauby  25 , Flavia Riccardo  8 , Alina Ivanciuc  9 , Verónica Gomez  10 , Ligita Jančorienė  26 , Gerd Xuereb  12   27 , Goranka Petrović  13 , Sierk Marbus  14 , Adela Vasili  15 , Kristin Tolksdorf  28 , Joanna Bogusz  17 , Beatrix Oroszi  18 , Lisa Domegan  19 , Lenka Součková  20 , Kimberley Marsh  21 , Sabrina Bacci  2 , Esther Kissling  23 ; I-MOVE & VEBIS Hospital Network teams
Collaborators, Affiliations
Multicenter Study

Vaccine effectiveness against influenza A in older adults and the effect of chronic conditions: results from the I-MOVE and VEBIS multicentre European hospital case-control studies, 2015/16-2023/24

Angela Mary Catherine Rose et al. BMC Med. .

Abstract

Background: The Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE/I-MOVE+) and Vaccine Effectiveness, Burden and Impact Studies (VEBIS) hospital networks have conducted seasonal multicentre, test-negative, case-control studies in Europe to measure influenza vaccine effectiveness (IVE) since 2015/16. We measured the effect of chronic conditions on VE of influenza A subtypes among older adults (≥ 65 years) using pooled-season data (2015/16-2023/24).

Methods: Hospital teams swabbed patients with severe acute respiratory infection (SARI) within 7 days of symptom onset. Cases were RT-PCR positive for influenza A(H1N1)pdm09 or A(H3N2); controls negative for any influenza virus. We calculated overall pooled-season IVE against influenza A(H1N1)pdm09 and A(H3N2), adjusted for study site, sex, age and onset date; and stratified by number of and by each chronic condition (diabetes, heart disease, lung disease/asthma, immunosuppression, kidney disease, liver disease, cancer, obesity). We investigated interaction between vaccination and each condition.

Results: We included 1805 A(H1N1)pdm09 cases with 16,329 controls; 2590 A(H3N2) cases with 14,920 controls, from 13 study sites (12 countries). Over all seasons, 63-67% cases and 70% controls had ≥ 2 chronic conditions. Against A(H1N1)pdm09, pooled-season IVE was 37% (95%CI: 29-44) overall; 49% (95%CI: 9-72), 30% (95%CI: 12-44) and 38% (95%CI: 29-46) in those with 0, 1, ≥ 2 chronic conditions. Most IVE point estimates were 34-45%, apart from immunosuppression (-7%), kidney disease (17%) and liver disease (54%), but 95% CIs overlapped. Significant interaction was observed for kidney disease (p = 0.02) and immunosuppression (p = 0.01). Against A(H3N2), pooled-season IVE was 17% (95%CI: 8-25) overall; 15% (95%CI: -26-42), 11% (95%CI: -8-27) and 18% (95%CI: 7-28) in those with 0, 1, ≥ 2 chronic conditions. Here, IVE point estimates ranged 13-25%, apart from immunosuppression (5%), kidney disease (6%) and liver disease (31%), although 95% CIs overlapped. There were no significant interactions.

Conclusions: Pooled-season results suggest low-moderate VE against influenza A subtypes among older SARI patients; higher against A(H1N1)pdm09 than A(H3N2), with little evidence of chronic condition modifying effect, apart from kidney disease and immunosuppression. We stress the importance of developing improved influenza vaccines for specific populations, and encourage further research into the effect of chronic conditions on IVE in older adults.

Keywords: Chronic conditions; Europe; Hospital; Influenza; Vaccine effectiveness.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The planning, conduct and reporting of the studies was in line with the Declaration of Helsinki. Official ethical approval was not required if studies were classified as being part of routine care/surveillance (Ireland, Italy, Malta, later seasons in Spain). In Belgium and Germany, VE is included in SARI surveillance. For Belgium, the study protocol was approved by the central Ethical Committee (CHU ST Pierre, Bruxelles) and each participating hospital’s local ethical committees in 2011 (AK/12-02-11/4111), and updated from 2014 (UZ-Brussel en VUB B.U.N. 143201215671). The German SARI surveillance was approved by the Charité-Universitätsmedizin Berlin Ethical Board (Reference EA2/218/19). Other study sites obtained local ethical approval from a national review board (Croatia: approved by the Ethics committee of the Croatian Institute of Public Health on 25 September 2015 (3-year approval), 21 November 2018, 7 November 2019, 26 November 2020, 24 May 2021, 26 January 2022, 20 June 2022 and 3 July 2023, Number 80-2661/1-15; Klasa: 030-02/18-01/1, Ur. broj 381-10-18-2; Klasa: 030-02/18-01/1, Ur.broj 381-15-19-4; Klasa:030-02/20-01/3, Ur.broj 381-15-20-2; Klasa:030-02/21-01/1, Ur.broj:381-15-21-7; Klasa:030-02/21-01/1, Ur.broj:381-15-22-14, Klasa: 030-02/22-01/2, Ur.broj:381-15-22-2, Klasa:030-02/23-01/3, Ur.broj: 117-15-23-3; Hungary: approved by the National Scientific and Ethical Committee (ETT/TUKEB 56025-3/2014/EKU; ETT/TUKEB 44088-3/2015/EKU; IV/1885‐5/2021/EKU); Lithuania: approved by Kaunas Regional Biomedical Research Ethics Committee for influenza seasons 2015-2020 (Nos P1-158200-04-476-138/2012, P2-158200-04-476-138/2012, P3-158200-04-476-138/2012, P4-158200-04-476-138/2012, P5-158200-04-476-138/2012, P6-158200-04-476-138/2012, P7-158200-04-476-138/2012), and approved by Lithuanian Bioethics Committee on 03 July 2020, and later permission extended for the study period for seasons 2020-2024, No. L-20-3/1-2; Navarre: approved by the Navarre Ethical Committee for Medical Research, Pyto2015/95 and EO2021/21; The Netherlands: the Dutch Medical Research Involving Human Subjects Act (Dutch acronym: WMO) did not apply, because only fully anonymous data were used and there were no interventions other than routine clinical care. A waiver for full medical ethical review was obtained from the Medical Ethical Committee of the University Medical Center Utrecht, reference No. WAG/om/15/034147; Portugal: approvals and/or amendments 22 May 2015, 28 September 2026, 12 December 2018, 28 April 2020, 19 January 2021, 7 June 2022 by the Ethics Committee of Instituto Nacional de Saúde Dr Ricardo Jorge, no registration number given; Romania: approved by the Ethics Committee of the Ministerul Apărării Naionale Institutul Naional de Cercetare pentru Dezvoltare Medico-Militară “Cantacuzino” for the period 2022–2023, No. CE199/2022; Spanish local sites for the I-MOVE periods (Donostia University Hospital, Virgen de las Nieves University Hospital from Granada, and Miguel Servet University Hospital from Zaragoza) obtained their ethical approvals for each season or protocol, from different ethic committees – Euskadi: PI2015104, 14 September 2015, Aragón: PI15/0123, 15 April 2015, with amendment 28 September 2016, Osakidetza: 20 November 2018, Aragón: PI19/430 01 April 2020, Andalucía: code f12f8377d78c34a25d6935eff535cd26715e2b8c, 15 April 2020). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Participating sites in the I-MOVE/I-MOVE + and VEBIS studies, 2015/16–2023/24. AL: Albania; BE: Belgium; CZ: Czechia; DE: Germany; ES: Spain (except Navarre Region); FI: Finland; FR: France; HR: Croatia; HU: Hungary; IE: Ireland; I-MOVE: Influenza – Monitoring Vaccine Effectiveness in Europe; IT: Italy; LT: Lithuania; MT: Malta; NA: Navarre Region, Spain; NL: the Netherlands; PL: Poland; PT: Portugal; RO: Romania; SC: Scotland; VEBIS: Vaccine Effectiveness, Burden and Impact Studies
Fig. 2
Fig. 2
Number of cases and controls over time, I-MOVE/I-MOVE+ and VEBIS studies, pooled influenza seasons 2015/16–2023/24, Europea. B: influenza B; H1: influenza A(H1N1)pdm09; H3: influenza A(H3N2); I-MOVE: Influenza – Monitoring Vaccine Effectiveness in Europe; VEBIS: Vaccine Effectiveness, Burden and Impact Studies. aLetters in parentheses indicate very small numbers of that type or subtype for that season. In the 2020/21 season there were no hospitalised cases reported from participating sites. As there were only two influenza B seasons with enough data from three or more sites/countries, we could not perform an influenza B pooled-season VE analysis
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