Morning influenza vaccination elicits superior antigen-specific immune responses in adults aged 60-85 years 2256881

Abstract Introduction Increasing evidence suggests that timing of vaccine administration affects immune responses, with some studies indicating that morning influenza vaccination (9:00-11:00) elicits a stronger antibody response than afternoon vaccination (15:00-17:00) in older adults. Existing trials focused on antibody responses, but did not assess induction of T-cell responses, which are also crucial for immunity to respiratory viruses and may contribute to time-of-day dependent vaccine effects. Methods Here, we analyzed data from the randomized controlled trial Chrono-Vax to determine the effect of influenza vaccination time on immune responses across a continuous time window from 9:00-17:00 in adults aged 60-85 years. Antigen-specific antibody titers and T-cell responses were measured before and one month after vaccination against three vaccine strains (A/H1N1, A/H3N2, and B/Victoria) with the hemagglutination inhibition and IFN-γ ELISpot assay, respectively. Results Antibody responses between the three randomized vaccination time groups (9:00-11:40, 11:40-14:20, 14:20-17:00) were compared using linear mixed effects models adjusted for baseline antibody titers. Vaccine strain-specific antibody responses were jointly analyzed within a single mixed-effects framework. Morning vaccination (9:00-11:40) resulted in a significantly greater fold increase in antibody titers than early and late afternoon vaccination (11:40-14:20, p = 0.005; 14:20-17:00, p = 0.009). Additionally, a generalized additive mixed model showed a significant effect of influenza vaccination timing on the antibody response (p = 0.012), with the strongest response estimated at 9:00. A similar pattern was observed for influenza-specific T-cell responses, though this effect did not reach statistical significance. Conclusion In summary, our findings indicate that morning influenza vaccination can enhance antibody responses in older adults, suggesting that tailored vaccination timing may improve protection against severe disease in this population. Funding Source This abstract is part of the BioClock Consortium (with project number 1292.19.077) of the research program NWA-ORC, which is (partly) financed by the Dutch Research Council (NWO). Additional funding was received from the Dutch Ministry of Health, Welfare Topic Categories Translational and Interventional Immunology (TI)