Two new analyses conclude that high-dose influenza vaccine is more effective against hospitalization and infection than the standard-dose version.
40% more effective against hospitalization
For the first study, published in The Lancet, an international group of researchers, including two from vaccine maker Sanofi, parsed pooled data from two large trials comparing the efficacy of the high-dose inactivated influenza vaccine (HD-IIV) with the standard-dose (SD-IIV) version against hospitalization for flu or pneumonia in older adults.
The FLUNITY-HD trial was an individual-level pooled analysis of two pragmatic randomized trials: DANFLU-2 in Denmark from 2022 to 2025 and GALFLU from 2023 to 2025 in Spain. In both trials, participants were randomly assigned to receive either HD-IIV or SD-IIV and followed, starting 2 weeks later to May 31 of the following year, in each flu season.
At an estimated 515 older adults needed to be vaccinated with HD-IIV instead of SD-IIV to prevent one all-cause hospitalisation, a simple switch from SD-IIV to HD-IIV could substantially reduce the burden of influenza on health systems.
FLUNITY-HD included 466,320 adults with an average age of 73.3 years; 48% were women, and 48.9% had one or more chronic conditions.
Hospitalization for flu or pneumonia was documented in 0.56% of the HD-IIV group, compared with 0.62% of SD-IIV recipients (relative vaccine effectiveness [rVE], 8.8%). HD-IIV also lowered the rate of cardiorespiratory hospitalization (2.02% vs 2.16% in the SD-IIV group; rVE, 6.3%), flu hospitalization (0.11% vs 0.16%; rVE, 31.9%), and all-cause hospitalization (8.54% vs 8.73%; rVE, 2.2%).
Hospital admission for flu occurred in 0.07% of HD-IIV participants and 0.12% in SD-IIV recipients (rVE, 39.6%), and hospitalization for pneumonia was documented in 0.50% and 0.51%, respectively (rVE, 2.3%).
Participants in both groups died of any cause with similar frequency (0.61% vs 0.62%; rVE, 1.2%). The rate of serious adverse events was comparable between groups (16,032 vs 15,857).
The findings “will inform evidence-based decision making by health-care providers, policy makers, and immunisation technical advisory groups, contributing to potential optimisation of influenza vaccination strategies in the vulnerable older adult population globally,” the authors wrote.
“At an estimated 515 older adults needed to be vaccinated with HD-IIV instead of SD-IIV to prevent one all-cause hospitalisation, a simple switch from SD-IIV to HD-IIV could substantially reduce the burden of influenza on health systems,” they added.
29% greater protection against infection
The second study, published in the International Journal of Infectious Diseases, used a test-negative design to analyze inpatient and outpatient data from four studies on older vaccinated adults tested for flu during the 2022-23 and 2024-25 flu seasons.
The average patient age was 81.1 years, 52.1% were women, and 87.2% had at least one chronic condition, primarily cardiovascular disease (74.2%), respiratory conditions (27.0%), and diabetes (18.7%).
In this integrated analysis, Italian older adults vaccinated with HD-IIV tended to report fewer laboratory-confirmed influenza episodes than their counterparts vaccinated with SD-IIV.
A total of 102 (8.2%) flu cases were identified, all but two (98.0%) of which were type A. Cases were almost evenly distributed among type A(H1N1)pdm09 (52.0%) and A(H3N2) (48.0%).
Of 1,238 participants, influenza positivity was lower among HD-IIV recipients than in the SD-IIV group (6.6% vs 10.3%; rVE, 29%). Relative to SD-IIV, HD-IIV was 54% more effective against infection among adults aged 80 years and older.
In the entire cohort, rVE of HD-IIV versus SD-IIV estimated using an unadjusted model was 40%, but when parsimoniously (28%) or fully (29%) adjusted, the estimate wasn’t statistically significant.
“In this integrated analysis, Italian older adults vaccinated with HD-IIV tended to report fewer laboratory-confirmed influenza episodes than their counterparts vaccinated with SD-IIV,” the researchers wrote. “This benefit was particularly evident in the oldest old, where the observed rVE consistently indicated a meaningful effect, regardless of the modeling strategy employed.”
