Background: The effectiveness of standard, egg-derived quadrivalent influenza vaccines (IIV4) may be reduced in adults ≥65 years of age, largely due to immunosenescence. An MF59?-adjuvanted trivalent influenza vaccine (aIIV3) and a high-dose trivalent influenza vaccine (HD-IIV3) offer older adults enhanced protection versus standard vaccines. This study compared the relative effectiveness of aIIV3 to IIV4 and HD-IIV3 in preventing influenza-related medical encounters over two US influenza seasons.

Methods: This retrospective cohort study included US patients ≥65 years vaccinated with aIIV3, IIV4, or HD-IIV3. The outcome of interest was the occurrence of influenza-related medical encounters. Data were derived from a large dataset comprised of primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness (rVE) was determined using the formula (% VE =1-ORadjusted)*100.

Results: In 2017-2018, cohorts included: aIIV3, n=524,223; IIV4, n=917,609; HD-IIV3, n=3,377,860. After adjustment, 2017-2018 rVE of aIIV3 vs. IIV4 was 18.2 (95% confidence interval [CI] 15.8 to 20.5); aIIV3 vs. HD-IIV3 was 7.7 (2.3 to 12.8). In 2018-2019, cohorts included: aIIV3, n=1,031,145; IIV4, n=915,380; HD-IIV3, n=3,809,601, with adjusted rVEs of aIIV3 vs. IIV4 of 27.8 (25.7 to 29.9) and vs. HD-IIV3 of 6.9 (3.1 to 10.6).

Conclusion: In the 2017-2018 and 2018-2019 influenza seasons in the US, aIIV3 demonstrated greater reduction in influenza-related medical encounters than IIV4 and HD-IIV3 in adults ≥65 years.