High-Dose Inactivated Influenza Vaccine Inconsistently Improves Heterologous Antibody Responses in an Older Human Cohort

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.