High dose inactivated influenza vaccine inconsistently improves heterologous antibody responses in an elderly 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 has 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 (HAI) antibody data from an influenza vaccine cohort spanning the 2013/14-2021/22 influenza seasons. We used this model to estimate the average causal effect (ACE) of obtaining the HD vaccine, relative to the SD 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.