High-dose influenza vaccination is associated with a reduced risk of hospitalization for pneumonia or influenza in older adults, regardless of immunosuppression status, according to a prespecified pooled analysis of the FLUNITY-HD study presented at ESCMID 2026.
High-dose inactivated influenza vaccine has demonstrated significant protection against laboratory-confirmed influenza cases and hospitalizations compared with the standard-dose vaccine in older adults, according to Dr Anne Marie Reimer Jensen from Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark.
However, the extent to which the high-dose influenza vaccine provides similar benefits for immunosuppressed individuals, who face a high burden of influenza-related complications, remains uncertain, she stated.
The FLUNITY-HD study, a pooled analysis of the DANFLU and GAFLU trials, evaluated 466,320 participants (mean age 73.3 years, 48 percent female), of whom 27,065 were classified as immunosuppressed. Participants were randomized in a 1:1 ratio to receive either a high- or standard-dose vaccine, administered as a single dose. [ESCMID 2026, abstract L0003]
Baseline characteristics were comparable between the immunosuppressed and no immunosuppressed subgroups, except for a higher prevalence of comorbidities, particularly cancer (>30 percent vs 11 percent) in the immunosuppressed group .
Immunosuppression was defined by the presence of immunosuppressive conditions (eg, haematologic disease, solid organ transplant, hematopoietic stem cell transplantation, primary immunodeficiency, or HIV) or immunosuppressive treatments (eg, chemotherapy [DANFLU-2 cohort only], immunosuppressive agents, or systemic glucocorticoids [GAFLU cohort only]).
At follow-up, patients who received a high-dose vaccine demonstrated a reduced risk of hospitalization for pneumonia or influenza, the study’s primary endpoint, with a relative vaccine effectiveness (rVE) of 8.8 percent, compared with those on a standard-dose vaccine.
This effect was consistently observed across immunosuppression status, with 16.4 percent of those with immunosuppression and 7.2 percent of those without immunosuppression.
In turn, immunosuppressed individuals had a greater absolute risk reduction in hospitalizations compared with non-immunosuppressed individuals (5.7 vs 0.7 per 1,000 person-years).
Jensen noted that despite a higher baseline risk associated with immunosuppression, the immunosuppressed cohort achieved an approximately eightfold greater absolute reduction in hospitalizations than the nonimmunosuppressed cohort. “This suggests a potentially greater absolute benefit among immunosuppressed participants,” said Jensen.
With regard to the secondary endpoints, high-dose vaccination was associated with a reduction in cardiorespiratory and laboratory-confirmed influenza hospitalizations (rVEs, 6.3 percent and 31.9 percent, respectively) compared with low-dose vaccination, regardless of immunosuppression status.
However, the effect on all-cause hospitalizations was modest, and there was no significant difference between the vaccine groups, Jensen noted.
“Overall, high-dose influenza vaccine reduced hospitalizations for pneumonia or influenza and cardiorespiratory and laboratory-confirmed influenza hospitalizations compared with standard-dose vaccine, with no effect modification by immunosuppression status,” concluded Jensen.