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 Global 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 Global 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 as 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 had 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 than 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 compared with standard-dose vaccine, with no effect modification by immunosuppression status,” concluded Jensen.