High-Dose Influenza Vaccine Reduces Hospitalizations in Adults 65 and Older

Recent clinical data and pooled analyses suggest that high-dose inactivated influenza vaccines provide superior protection against severe clinical outcomes for adults aged 65 years and older compared to standard-dose vaccines.

The findings highlight a reduction in hospitalizations for influenza, pneumonia, and other cardiorespiratory complications among older populations, including those with comorbid conditions such as diabetes.

Evidence from Large-Scale Clinical Trials

A pooled analysis of two large pragmatic randomized clinical trials, involving 465,400 participants aged 65 years and older, concluded that the high-dose vaccine demonstrated superior protection against hospitalizations for influenza, pneumonia, and other causes.

In a separate registry-based, open-label, randomized, active-controlled trial conducted in Galicia, Spain, researchers evaluated the effectiveness of the high-dose vaccine across the 2023-2024 and 2024-2025 influenza seasons.

This Spanish study included 103,169 unique participants with a mean age of 72.3 years. The primary end point was a composite of hospitalization for influenza or pneumonia starting 14 days after vaccination through May 31 of the following year.

The results showed that a primary end-point event occurred in 174 of 67,093 participants (0.26% absolute risk) in the high-dose group, compared to 227 of 66,789 participants (0.34% absolute risk) in the standard-dose group.

This represents a relative vaccine effectiveness of 23.7%, with a 95% confidence interval ranging from 6.6 to 37.7.

Impact on High-Risk Groups and Cardiovascular Health

Additional research from Copenhagen University Hospital, published in JAMA Internal Medicine, analyzed more than 332,000 older adults in Denmark across three flu seasons from 2022–23 through 2024–25.

The analysis specifically tracked participants with and without diabetes, noting that approximately 44,000 individuals (13% of the group) had diabetes.

The high-dose inactivated influenza vaccine (HD-IIV) contains four times the amount of antigen found in standard-dose vaccines (SD-IIV). The study found that HD-IIV was associated with reductions in hospitalizations for several categories:

• Influenza: Relative vaccine effectiveness (rVE) of 41.6% for those with diabetes and 44.3% for those without diabetes.
• Cardiovascular disease: rVE of 12.0% for those with diabetes and 6.0% for those without diabetes.
• Cardiorespiratory disease: rVE of 7.4% for those with diabetes and 5.3% for those without diabetes.

While the protective benefits were similar across both groups, researchers noted that the high-dose vaccine may confer a greater absolute benefit to people with diabetes, who are at an elevated risk for flu-related complications.

Broader Health Implications

Beyond the reduction of acute respiratory hospitalizations, other reports indicate a potential link between high-dose inactivated influenza vaccines and a lower risk for dementia among older adults.

The combination of these findings suggests that the increased antigen content in high-dose vaccines may address the diminished immune response often seen in the elderly, leading to better outcomes for both respiratory and systemic health.

Despite these findings, some correspondence in The Lancet, published on April 11, 2026, has raised questions regarding the clarity of the benefits associated with higher doses of influenza vaccines.