The effect of the time of day of influenza vaccination on antibody and T-cell responses in older adults

Abstract Increasing evidence suggests that time of day of vaccine administration affects immune responses. We aimed to determine the optimal time of day for influenza vaccination by characterising temporal patterns in vaccine-induced immune responses. Additionally, we assessed the effect of vaccination time relative to an individual’s circadian phase on immune responses. A randomised controlled trial was conducted with 278 participants aged 60–85 years, who received influenza vaccination at a randomised time between 09:00 and 17:00. Antigen-specific antibody titers and T-cell responses to three vaccine strains (A/H1N1, A/H3N2 and B/Victoria) were measured pre- and one month post-vaccination. A permutation-based test was used to determine differences in strain-specific immune responses between the three randomisation time blocks (09:00–11:40, 11:40–14:20, 14:20–17:00). As a secondary analysis, strain-specific immune responses were jointly analysed in a single generalised additive mixed-effects model (GAMM) to assess the overall impact of influenza vaccination timing. The permutation-based test found no significant differences in immune responses between the three vaccination time blocks. A GAMM revealed that morning vaccination resulted in significantly higher antibody responses across strains than early afternoon vaccination( p = 0.045), but not late afternoon vaccination ( p = 0.498). Antibody responses displayed a non-significant non-linear pattern from 09:00 to 17:00, with the model suggesting highest responses in participants vaccinated at 09:00. A similar trend was observed for T-cell responses. Irrespective of chronotype, vaccinations administered at the start of an individual’s day tended to elicit the strongest vaccine-induced immune responses. Although statistical evidence for a time-of-day effect was limited, numerically higher antibody and T-cell responses were consistently observed in the morning group.