Relative effectiveness of high dose versus standard dose influenza vaccines in older adult outpatients over four seasons, 2015-16 to 2018-19

Background: New influenza vaccine formulations are designed to improve vaccine effectiveness and protect those most vulnerable to infection. High dose trivalent inactivated influenza vaccine (HD-IIV3), licensed for ages >= 65 years, produces greater antibody responses and efficacy in clinical trials, but post-licensure vaccine effectiveness (VE) compared to standard dose (SD-IIV3/4) vaccine remains an open question. Methods: Using a test-negative, case control design and propensity analyses to adjust for confounding, US Influenza VE Network data from the 2015-2016 through 2018-2019 seasons were analyzed to determine relative VE (rVE) between HD-IIV3 and SD-IIV3/4 among outpatients >= 65 years old presenting with acute respiratory illness. Influenza vaccination status was derived from electronic medical records and immunization registries. Results: Among 3861 enrollees, 2993 (78%) were vaccinated; 1573 (53%) received HD-IIV3 and 1420 (47%) received SD-IIV3/4. HD-IIV3 recipients differed from SD-IIV3/4 recipients by race, previous vaccination, number of outpatient visits in the previous year and timing of vaccination, and were balanced in the propensity model except the timing of vaccination. Compared with no vaccination, significant protection against any influenza A was observed from both HD-IIV3 (VE = 29%; 95%CI = 10%, 44%) and SD-IIV3/4 (VE = 24%; 95%CI = 5%, 39%); rVE = 18% (95%CI = 0%, 33%, SD as referent). When stratified by virus type, against A/H1N1, HD-IIV3 VE was 30% (95%CI = -7%, 54%), SD-IIV3/4 VE was 40% (95%CI = 10%, 61%), and rVE = -32%; (95%CI = -94%, 11%); Against A/H3N2, HD-IIV3 VE was 31% (95%CI = 9%, 47%), SD-IIV3/4 VE was 19% (95%CI = -5%, 37%), and rVE = 27%; (95% CI = 9%, 42%). Conclusions: Among adults >= 65 years of age, recipients of standard and high dose influenza vaccines differed significantly in their characteristics. After adjusting for these differences, high dose vaccine offered more protection against A/H3N2 and borderline significant protection against all influenza A requiring outpatient care during the 2015-2018 influenza seasons. (C) 2020 Elsevier Ltd. All rights reserved.