Loading ...

TOPLINE:

Among older adults, high-dose inactivated influenza vaccine (HD-IIV) was associated with lower risks for hospitalizations for influenza, laboratory-confirmed influenza, pneumonia or influenza, cardiorespiratory disease, and all causes than standard-dose IIV (SD-IIV).

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of randomized clinical trials to compare the efficacy of HD-IIV with that of SD-IIV in preventing hospitalization and mortality in older adults.
• They searched PubMed and Embase databases for studies published from December 2009 to September 2025 and included trials conducted over at least one influenza season; trials conducted during influenza pandemics were excluded.
• Eight trials involving 605,098 participants were included, comprising five trials that enrolled adults aged 65 years or older from the general population, two that enrolled nursing home residents aged 65 years or older, and one that enrolled patients with heart failure or a history of myocardial infarction.
• Outcomes were hospitalizations for influenza, laboratory-confirmed influenza, pneumonia or influenza, cardiorespiratory disease, and all causes as well as all-cause mortality; the primary analyses focused on adults aged 65 years or older.

TAKEAWAY:

• HD-IIV was associated with a reduced risk for hospitalizations for influenza compared with SD-IIV, with a combined relative vaccine effectiveness (rVE) of 38.5% (95% CI, 26.5%-48.5%) across seven trials.
• For hospitalizations due to laboratory-confirmed influenza, HD-IIV was linked to a reduced risk compared with SD-IIV (combined rVE, 31.2%; 95% CI, 19.3%-41.4%) across three trials.
• HD-IIV was also associated with a reduced risk for hospitalizations for pneumonia or influenza (rVE, 11.5%; 95% CI, 5.9%-16.8%) and cardiorespiratory disease (rVE, 7.5%; 95% CI, 4.7%-10.3%) across eight trials and a reduced risk for all causes (rVE, 3.3%; 95% CI, 1.8%-4.8%) across seven trials.
• Across eight trials, no significant difference in all-cause mortality was observed between the HD-IIV and SD-IIV groups.

IN PRACTICE:

“Overall, these findings demonstrate the clinical benefits of HD-IIV in lowering hospitalization risk, underscoring its value in reducing influenza burden among older adults and the corresponding impact across health systems,” the authors wrote. 

“These findings may inform decision-makers in developing vaccine recommendations and policies,” they added.

SOURCE:

The study was led by Kristoffer Grundtvig Skaarup, MD, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark. It was published online on May 26, 2026, in JAMA Network Open.

LIMITATIONS:

Small-study effects were observed for pneumonia or influenza hospitalization, all-cause hospitalization, and all-cause death outcomes. The combined estimates of rVE for influenza and laboratory-confirmed influenza hospitalizations were largely driven by the DANFLU-2 and GALFLU trials, which enrolled participants from Denmark and Galicia, Spain, potentially affecting generalizability of the findings. Moreover, the pooled effect sizes reflected average population-level estimates and may not directly translate to individual-level protection.

DISCLOSURES:

This study was funded by Sanofi SA. Three authors reported being employees of Sanofi SA, and one of them also reported holding shares in the company. Several authors disclosed receiving grant support, travel reimbursement, speaker or personal fees, serving on advisory boards, and other ties with multiple pharmaceutical companies, including Sanofi SA.

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