Abstract Background In 2022, the US Advisory Committee on Immunization Practices (ACIP) recommended adults ≥65 years receive adjuvanted or higher-dose influenza vaccines. Increased uptake following this recommendation enabled the estimation of season-specific relative vaccine effectiveness (rVE) using a test-negative design (TND). A 2022–23 season TND study found comparable effectiveness of adjuvanted (aQIV) and high-dose quadrivalent influenza vaccine (HD-QIV) against test-confirmed influenza. Expanding on prior evidence, this study evaluated the rVE of aQIV vs. HD-QIV in preventing test-confirmed influenza during 2023–24, including hospitalizations in overall and high-risk older adults in a pooled analysis with 2022–23.Figure 1.Study Design.Figure 2.Adjusted rVE of aQIV vs. HD-QIV in preventing test-confirmed influenza. Methods This retrospective TND study included US adults ≥65 years vaccinated with aQIV or HD-QIV who presented with acute respiratory or febrile illness in any setting or emergency department (ED)/inpatient settings (Figure 1). rVE was also evaluated in the inpatient only setting through a pooled analysis of 2022–23 and 2023–24 seasons. A subgroup pooled analysis additionally estimated rVE in inpatient settings in patients with ≥1 high-risk conditions. A doubly robust model was used, combining inverse probability of treatment weighting and logistic regression to adjust for potential confounders. Results 37,377 vaccinated patients were included (3,174 positive cases and 34,203 negative controls). Comparable effectiveness between aQIV and HD-QIV was observed in preventing test-confirmed influenza with a rVE of -0.9% (95% CI: -9.9, 7.3) in any setting and 0.5% (-12.1, 11.6) in ED/inpatient settings (Figure 2). Similarly, comparable effectiveness was observed in the pooled inpatient only analysis in both the overall (-0.5% -13.4, 10.9) and high-risk subgroup (-1.3% -14.4, 10.4) (Figure 2). Conclusion Consistent with prior evidence, these results demonstrate comparable effectiveness between aQIV and HD-QIV for preventing test-confirmed influenza in any or ED/inpatient settings among adults ≥65 years during the 2023–24 season. Additionally, pooled analyses for the 2022-23 and 2023-24 seasons showed comparable effectiveness between aQIV and HD-QIV for hospitalizations, in overall and high-risk older adults. Disclosures Mahrukh Imran, MScPH, CSL Seqirus: Grant/Research Support|CSL Seqirus: Stocks/Bonds (Private Company) Benjamin Chastek, MS, Optum (UnitedHealth Group): Stocks/Bonds (Public Company) Tim Bancroft, PhD, Optum: I am an employee of Optum. Optum was paid by Seqirus for this work. My employment at Optum is not contingent upon this work. Stephen I. Pelton, MD, CSL Seqirus: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Merck Vaccines: Grant/Research Support|Merck Vaccines: Honoraria|Pfizer, Inc.: Grant/Research Support|Pfizer, Inc.: Honoraria|Sanofi: Honoraria|Sanofi: DSMB, Adjudicator for RSV vaccine trial Mendel Haag, PhD, PharmD, CSL Seqirus: Grant/Research Support|CSL Seqirus: Stocks/Bonds (Private Company) Ian McGovern, MPH, CSL Seqirus: Grant/Research Support|CSL Seqirus: Stocks/Bonds (Private Company)
Imran et al. (2026) studied this question.