Adjuvanted and high-dose flu vaccines protect older adults equally well

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.May 20 2026

A large Kaiser Permanente Northern California study found that two enhanced flu vaccines performed similarly in adults aged 65 years or older, supporting flexible vaccine choices for a population at high risk of influenza complications.

Study: Adjuvanted vs High-Dose Influenza Vaccines in Older US Adults. Image Credit: FaceStock / Shutterstock

In a recent study published in the journal JAMA Network Open, researchers compared adjuvanted and high-dose influenza vaccines for adults aged 65 years or older.

Older Adult Influenza Vaccine Background

Every year, seasonal influenza causes millions of illnesses, but older adults face the greatest risk. In the United States, nearly 70%-85% of influenza-related deaths occur in people aged 65 years or older, thus highlighting the need for effective vaccination efforts within this high-risk population. To improve immunity against seasonal influenza, adjuvanted and high-dose vaccines are recommended for use in older adults.

Previous studies have shown that enhanced influenza vaccines provide superior protection against seasonal influenza relative to standard-dose vaccines; however, adjuvanted and high-dose vaccines have not been compared in a pragmatic randomized study.

Understanding whether one vaccine performs better could guide vaccination policies, reduce hospitalizations, and improve healthy aging outcomes. Further research is needed to confirm relative effectiveness across multiple influenza seasons.

Cluster Randomized Vaccine Study Design

Researchers conducted a large cluster randomized crossover study within Kaiser Permanente Northern California, an integrated health care system serving approximately 4.6 million individuals. The study participants were 65 years of age or older and had received either an adjuvanted inactivated influenza vaccine or a high-dose inactivated influenza vaccine between August 17, 2023, and April 16, 2024. Those people who tested positive for influenza before obtaining full protection from the vaccine were excluded.

A total of 65 medical facilities participated in this research project. During the first week of the vaccination season, approximately half of the facilities administered the adjuvanted vaccine while the remaining facilities administered the high-dose vaccine. Throughout the flu season, the same week-to-week alternating administration of the two vaccine formulations took place at each medical clinic. This was intended to provide a balanced exposure to both vaccines while reflecting today's clinical practice.

Participants were considered fully vaccinated 14 days after immunization. Polymerase chain reaction (PCR) testing confirmed the diagnosis of influenza in any clinical setting as the primary outcome. Secondary outcomes included influenza-related hospitalizations or emergency department visits, and hospitalizations for community-acquired pneumonia. The researchers used Cox proportional hazards regression, adjusting for age, sex, race and ethnicity, comorbidities, prior vaccination history, and health care utilization.

Influenza Vaccine Effectiveness Results

The study included 429,595 older adults with an average age of 75 years. Among them, 212,875 individuals received an adjuvanted influenza vaccine, and 216,720 subjects received a high-dose vaccine. The study population was racially and ethnically diverse and broadly representative of Kaiser Permanente Northern California members, although the authors noted that some lower-income groups may be underrepresented. Baseline health status, vaccination history, and prior health care utilization were similar between the two groups, ensuring accurate comparisons.

Seasonal trends indicated that influenza peaked in late December 2023, as in national seasonal trends. A total of over 45,000 individuals received PCR tests for influenza, with 1,703 positive results. There were no significant differences in testing rates between the two vaccine groups, alleviating concerns about potential bias due to one group being more inclined to seek medical attention or testing.

Among recipients of the adjuvanted vaccine, 836 individuals developed laboratory-confirmed influenza, corresponding to 3.93 cases per 1,000 persons. In the high-dose vaccine group, 867 individuals had influenza cases, for a rate of 4.00 cases per 1,000 persons.

The majority of patients in both groups with confirmed cases had influenza A rather than influenza B. The relative effectiveness of the adjuvanted vaccine compared to the high-dose vaccine was estimated at 1.5%, and confidence intervals indicated no significant difference in relative effectiveness between the two vaccines.

Hospitalization and Pneumonia Outcome Findings

The vaccine's effectiveness against serious outcomes of influenza was also assessed in this study. Among people receiving the adjuvanted vaccine, there were 411 cases of influenza-related hospitalization or emergency department visits, compared with 466 in the high-dose group. Relative vaccine effectiveness against these severe outcomes was estimated at 9.1%, but the confidence interval again showed no meaningful statistical difference.

Hospitalizations for community-acquired pneumonia were similarly comparable between groups. The relative vaccine effectiveness estimate for hospitalization due to community-acquired pneumonia was 1.0%, supporting comparable protection, although the study was not designed to prove identical protection against pneumonia-related hospitalizations. Additional sensitivity analyses accounting for facility differences and vaccination timing produced results consistent with the primary analysis.

These findings are important because older adults are particularly vulnerable to complications such as pneumonia, hospitalization, and death during influenza seasons. The results suggest that both enhanced vaccines provide comparable protection, giving clinicians and health systems flexibility in vaccine selection.

Consequently, this could facilitate vaccine availability and simplify how public health approaches vaccination during future influenza outbreaks. However, the study did not compare either vaccine with no vaccination, was conducted within a single integrated Northern California health system, and may not generalize to uninsured populations or to regions outside Northern California.

The authors also noted that this was the first season of an ongoing two-season study, with further evidence expected from the second season.

Older Adult Flu Vaccination Implications

The study shows that adjuvanted and high-dose influenza vaccines provided similar protection against laboratory-confirmed influenza, influenza-related hospitalization, emergency department visits, and community-acquired pneumonia in adults aged 65 years or older.

Neither of these vaccination methods had statistically better effectiveness than the other in 2023-2024. Therefore, the data support continuing existing recommendations that both types of influenza vaccines are reasonable options for vaccinating older adults, highlighting the need to maintain high vaccination coverage among older adults, since influenza remains a significant burden on health care systems and at-risk communities worldwide.

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