This study states that Approaches to overcome suboptimal immune responses include adding an adjuvant to the vaccine, such as in the MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3; Fluad, Seqirus USA Inc., Summit, NJ, USA), and increasing the antigenic content per vaccine dose, as represented by high-dose nonadjuvanted trivalent inactivated influenza vaccine (HD-IIV3; Fluzone High-Dose, Sanofi Pasteur Inc., Swiftwater, PA, USA) [10, 11]. Both vaccines are currently licensed and available for use in the United States and across the globe such as in the United Kingdom, Canada, Europe, and Australia. Studies have shown that the efficacy and effectiveness of HD-IIV3 are greater than that of nonadjuvanted, standard-dose vaccines in adults ≥65 years, as is the effectiveness of aIIV3 in this population. Studies have also demonstrated that aIIV3 induces the production of cross-reactive antibodies and thus may provide heterotypic protection [23–26].

The vaccine effectiveness of aIIV3 relative to enhanced and standard vaccines has been estimated in few comparative studies with a limited sample size. A retrospective cohort study using a large integrated dataset was thus designed to assess the relative vaccine effectiveness (rVE) of aIIV3 versus nonadjuvanted influenza vaccines (IIV4 and HD-IIV3) in preventing influenza-related medical encounters during the 2017–2018 and 2018–2019 influenza seasons in the United States.

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