Estimating standard-dose and high-dose Fluzone vaccine efficacies for influenza A based on HAI titers

Background: The high-dose (HD) Fluzone influenza vaccine is currently recommended for individuals 65 and older, since it was shown in past studies to improve antibody responses and vaccine efficacy (VE) compared to a standard-dose (SD) formulation. Since influenza vaccines are frequently reformulated, monitoring any potential changes in VE is crucial. Traditional efficacy trials can be costly and time-consuming. Conducting immunogenicity studies with updated formulations and estimating VE with the resulting data is a more efficient way to assess these vaccines over time. Hemagglutination inhibition (HAI) titers are considered a reliable correlate of protection in influenza vaccine research and have previously been used to estimate VE.

Methods: We analyzed data from a human vaccine cohort who received either the SD or HD Fluzone split-inactivated influenza vaccine during influenza seasons 2013/14 to 2021/22. We used a previously developed statistical model to map pre- and post-vaccination HAI titers to protection probabilities, and computed differences in vaccine efficacy (VE) of the HD vaccine in older ( 65 years) populations compared to SD vaccines in the same age group and in younger (<65 years) adults.

Results: We found that for participants aged 65 and older, the HD vaccine generally improved the estimated VE across seasons. However, we also found that HD recipients often had a lower estimated VE than younger SD recipients.

Conclusions: While HD Fluzone vaccines lead to a small increase in estimated VE compared to SD in older adults, further increases in dose or other developments to improve VE should be considered.