Comparative Effectiveness of Adjuvanted and High-Dose Influenza Vaccines

Overview

This study evaluated the relative vaccine effectiveness (rVE) of adjuvanted quadrivalent influenza vaccine (aQIV) versus high-dose quadrivalent influenza vaccine (HD-QIV) in adults aged ≥65 years during the 2023–2024 season and in pooled 2022–2024 hospitalization analyses. The findings showed comparable effectiveness between the two vaccines against test-confirmed influenza, including hospitalization outcomes in overall and high-risk older adults.

Background

Influenza poses a substantial health burden in adults aged ≥65 years, who account for a disproportionate share of influenza-related hospitalizations and deaths. Immunosenescence can diminish vaccine responses in older adults, contributing to the development and use of enhanced influenza vaccines formulated with an adjuvant or higher antigen dose.

Data Highlights

• The 2023–2024 analysis included 37,377 vaccinated and tested adults aged ≥65 years, including 3174 influenza-positive cases and 34,203 test-negative controls.

• In 2023–2024, rVE of aQIV versus HD-QIV was −0.9% (95% CI, −9.9 to 7.3; P = 0.83) in any setting.

• In ED/hospitalization settings, rVE was 0.5% (95% CI, −12.1 to 11.6; P = 0.94).

• In pooled 2022–2024 hospitalization analyses, rVE was −0.5% (95% CI, −13.4 to 10.9; P = 0.94) overall and −1.3% (95% CI, −14.4 to 10.4; P = 0.84) among adults with ≥1 high-risk condition.

Key Findings

• aQIV and HD-QIV showed no statistically significant differences in effectiveness against test-confirmed influenza in any evaluated analysis.

• Comparable effectiveness was observed in any setting and in ED/hospitalization settings during the 2023–2024 season.

• Pooled 2022–2024 analyses showed comparable effectiveness against test-confirmed influenza hospitalizations in both the overall population and adults with ≥1 high-risk condition.

• The prior 2022–2023 analysis reported rVE of −2.5% in any setting and 0.0% in ED/hospitalization settings, findings that were consistent with the comparable effectiveness observed in the current study.

• The study used Optum Market Clarity electronic health records and administrative claims data.

• The source notes that ACIP preferentially recommends adjuvanted or higher-dose influenza vaccines over standard-dose unadjuvanted vaccines for adults aged ≥65 years.

Clinical Implications

For adults aged ≥65 years, the study supports comparable effectiveness of aQIV and HD-QIV against test-confirmed influenza outcomes, including hospitalization. These findings are consistent with previous comparative studies and current recommendations favoring enhanced influenza vaccines for older adults.

Conclusion

aQIV and HD-QIV provided comparable protection against test-confirmed influenza among adults aged ≥65 years during the 2023–2024 season. Pooled analyses of the 2022–2023 and 2023–2024 seasons likewise showed comparable effectiveness against test-confirmed influenza hospitalizations in both the overall and high-risk older adult populations.

Related Resources & Content

1. Domnich A, de Waure C. Comparative effectiveness of adjuvanted versus high-dose seasonal influenza vaccines for older adults: a systematic review and meta-analysis. Int J Infect Dis. 2022;122:855-863.

2. Imran M, Chastek B, Bancroft T, Webb N, Pelton SI, Haag MDM, et al. Comparable effectiveness of MF59-adjuvanted and high-dose quadrivalent inactivated influenza vaccines for prevention of test-confirmed influenza during the 2022-2023 influenza season. Int J Infect Dis. 2025;159:107983.

3. McGovern I, Chastek B, Bancroft T, Webb N, Imran M, Pelton SI, et al. Relative vaccine effectiveness of MF59-adjuvanted vs high-dose trivalent inactivated influenza vaccines for prevention of test-confirmed influenza hospitalizations during the 2017-2020 influenza seasons. Int J Infect Dis. 2024;146:107160.

4. Grohskopf LA, Ferdinands JM, Blanton LH, Broder KR, Loehr J. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2024-25 influenza season. MMWR Recomm Rep. 2024;73:1-25.

5. Hsiao A, Leong T, Fireman B, Hansen J, Zerbo O, Jacobson KB, et al. Adjuvanted vs high-dose influenza vaccines in older US adults: a cluster randomized crossover study. JAMA Netw Open. 2026;9:e2610120.

6. Ferdinands JM, Blanton LH, Alyanak E, Chung JR, Trujillo L, Taliano J, et al. Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: a systematic review and network meta-analysis. J Am Geriatr Soc. 2024;72:3875-3889.