Abstract
BACKGROUND: Older adults often mount a weak immune response to standard inactivated influenza vaccines. To induce a stronger response and better protection, a high-dose (HD) version of the inactivated Fluzone vaccine is recommended for individuals >65 years of age. While better immunogenicity and protection against the vaccine strain have been shown, it is not known if the HD vaccine also induces a robust antibody response to heterologous strains. METHODS: We fit bayesian multilevel regression models to hemagglutination inhibition antibody data from an influenza vaccine cohort spanning the influenza seasons of 2013-2014 to 2021-2022. We used this model to estimate the average causal effect of obtaining the HD vaccine relative to the standard-dose vaccine. RESULTS: We show that while there is generally a benefit derived from the HD vaccine, the impact is small and inconsistent. For some strains, the HD vaccine might even result in less robust heterologous responses. CONCLUSIONS: We suggest that further increases in dose might be worth investigating to help induce a stronger broad response.