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Traditional influenza vaccines may be less immunogenic in adults ≥65 years of age due to immunosenescence. Two influenza vaccines-MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose influenza vaccine (HD-IIV3)-were developed to overcome this problem. We summarize estimates of the relative vaccine effectiveness (rVE) of aIIV3 vs. HD-IIV3 and aIIV3 vs. standard, egg-based quadrivalent influenza vaccines (IIV4e) during the 2017-2018, 2018-2019, and 2019-2020 US influenza seasons using the same underlying electronic medical record and linked claims dataset for all three seasons. The primary outcome was influenza-related medical encounters (IRMEs), defined by diagnostic codes specific to influenza (ICD J09*-J11*). rVE was estimated using propensity score methods adjusting for demographics and health status. rVE estimates demonstrated consistent benefit for aIIV3 over IIV4e in the overall and at-risk populations. Relative to HD-IIV3, aIIV3 provided improved benefit in the overall study population and comparable benefit in the at-risk population across each season.

Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine over Three Consecutive Influenza Seasons in the United States