Which is better? Adjuvanted versus high-dose influenza vaccine in older adults

The burden of influenza is greatest in older adults (≥ 65 years of age), as this age group is at increased risk of developing influenza infection and complications.1 Studies have shown that adjuvanted or higher-dose formulations of influenza vaccine elicit an improved immune response and better protection in older adults when compared with standard-dose influenza vaccines.1 Canadian and US influenza guidelines preferentially recommend high-dose or adjuvanted influenza vaccines over other influenza vaccines for adults 65 years of age or older.1,2 However, the comparative effectiveness of adjuvanted versus high-dose influenza vaccines in older adults has not been assessed in a real-world randomized study.To examine this issue, U.S. researchers assessed the relative vaccine effectiveness of adjuvanted influenza vaccine (Fluad) vs high-dose inactivated influenza vaccine (Fluzone High-Dose or a recombinant influenza vaccine [not available in Canada]) against polymerase chain reaction (PCR)-confirmed influenza in older adults at Kaiser Permanente Northern California (KPNC). The cluster randomized crossover study was conducted during the 2023–2024 influenza season, although the study continued into the following flu season. Sixty-five 65 KPNC facilities were cluster randomized, such that approximately half of facilities administered adjuvanted and half high-dose influenza vaccine on the first week of the vaccination season. Thereafter, every facility crossed over and alternated formulations weekly.1 The investigators used Cox proportional hazards regression to estimate the relative vaccine effectiveness of adjuvanted versus high-dose influenza vaccine, adjusted for age, sex, race and ethnicity, comorbidities and healthcare utilization. The study included all adults 65 years of age or older who were vaccinated with adjuvanted or high-dose inactivated influenza vaccine during routine care at a KPNC facility between August 17, 2023 and April 16, 2024.1The primary outcome was PCR-confirmed influenza in any clinical setting. Secondary outcomes were PCR-confirmed influenza with hospitalization or emergency department visits and hospitalization for community-acquired pneumonia. Outcomes were assessed starting October 1, 2023, or 14 days after vaccination, whichever came later.1Key resultsThe study included 429,595 individuals from the 2023–2024 influenza season (mean age 75 years; 55.1% female).212,875 (49.6%) individuals received adjuvanted influenza vaccine and 216,720 (50.4%) received high-dose influenza vaccine. 836 cases of PCR-confirmed influenza (3.9 per 1000 persons) were identified after adjuvanted influenza vaccine and 867 cases (4.0 per 1000 persons) after high-dose influenza vaccine. For the primary outcome (PCR-confirmed influenza in any clinical setting), the adjuvanted influenza vaccine was noninferior to high-dose influenza vaccine, with an adjusted relative vaccine effectiveness of 1.5% (95%CI, −8.4% to 10.5%; noninferiority P < .001).For the secondary outcomes, the relative vaccine effectiveness of adjuvanted vs high-dose influenza vaccine was 9.1% (95%CI, −4.0% to 20.4%; noninferiority P < .001) against PCR-confirmed influenza with hospitalization or ED visits, and 1.0% (95%CI, −11.4% to 12.0%; noninferiority P < .001) against hospitalization for all-cause community-acquired pneumonia.1The authors conclude that in the first (2023–2024) season of this large ongoing study in adults 65 years or older, adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza in any clinical setting. In addition, the adjuvanted vaccine was noninferior to the high-dose vaccine in effectiveness against PCR-confirmed influenza with hospitalization or emergency department visits, and against hospitalizations for community-acquired pneumonia. These results support the equivalency of adjuvanted and high-dose influenza vaccines for adults 65 years of age or older.1References:Hsiao A, Leong T, Fireman B, et al. Adjuvanted vs high-dose influenza vaccines in older US adults. A cluster randomized crossover study. JAMA Network Open 2026;9(5):e2610120. (accessed May 12, 2026).National Advisory Committee on Immunization (NACI). An Advisory Committee Statement (ACS). Statement on seasonal influenza vaccines for 2025–2026. (accessed May 12, 2026).

Which is better? Adjuvanted versus high-dose influenza vaccine in older adults

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