TOPLINE:

In a pooled analysis, the high-dose inactivated influenza vaccine provided superior protection compared with the standard-dose vaccine against hospitalisations for influenza or pneumonia; it also reduced rates of hospitalisations for any cardiorespiratory disease, hospitalisations for laboratory-confirmed influenza, and all‑cause hospitalisations.

METHODOLOGY:

• Researchers conducted a pooled analysis of two harmonised randomised trials ─ DANFLU‑2 and GALFLU ─ to assess the relative vaccine effectiveness (rVE) of high‑dose vs standard‑dose inactivated influenza vaccines in older adults during the 2022-2025 and 2023-2025 seasons, respectively.
• The analysis included 466,320 older adults (mean age, 73.3 years; 48% women), of whom 233,311 received a single intramuscular high‑dose vaccine (60 μg haemagglutinin per strain) and 233,009 received a single intramuscular standard‑dose vaccine (15 μg haemagglutinin per strain).
• The trials' primary outcome was hospitalisation for influenza or pneumonia; secondary outcomes included hospitalisations for any cardiorespiratory disease, hospitalisations for laboratory-confirmed influenza, all‑cause hospitalisations, and all‑cause mortality.
• Participants were followed up from 14 days after vaccination until May 31 of the following year for each season, with routine healthcare databases serving as primary data sources.

TAKEAWAY:

• Hospitalisations for influenza or pneumonia occurred in 0.56% of participants who received the high‑dose vaccine vs in 0.62% of those who received the standard-dose vaccine (unadjusted rVE, 8.8%; P = .0082).
• The incidence of hospitalisations for any cardiorespiratory disease was lower with the high-dose vaccine than with the standard-dose vaccine (rVE, 6.3%; P = .0006), as was the rate of hospitalisations for laboratory-confirmed influenza (rVE, 31.9%; P < .0001).
• The rate of all-cause hospitalisations was lower with the high‑dose vaccine (rVE, 2.2%; P = .012), whereas the rate of all‑cause mortality did not differ significantly between groups.
• A total of 16,032 serious adverse events occurred in the high‑dose arm and 15,857 such events in the standard‑dose arm. Findings were similar across subgroups defined by age, sex, and chronic conditions.

IN PRACTICE:

"These results provide further evidence that widespread adoption of HD-IIV [high-dose inactivated influenza vaccine] could substantially reduce the burden of influenza on both older adults and health-care systems globally," the authors wrote.

SOURCE:

The study was led by Niklas Dyrby Johansen, MD, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark. It was published online on October 17, 2025, in The Lancet.

LIMITATIONS:

The individual trials had an open‑label design and did not include systematic influenza testing and data on race and ethnicity. Using routine healthcare databases as primary data sources may have introduced imprecision into trial data. In addition, high rates of COVID vaccine co‑administration in both trials may have complicated the assessment of adverse events.

DISCLOSURES:

The study was funded by Sanofi. Five authors disclosed being full-time employees of Sanofi and possibly holding shares and/or stock options in the company. Several authors reported receiving speaker or lecture fees, research grants, or consulting fees; serving on advisory boards; or having other relationships with various healthcare and pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.