A Pilot Study Exploring the Effects of Circadian Phase on Influenza Vaccination Antibody Responses

Objective: Conventional investigations into vaccination scheduling have relied on fixed clock time, which fails to account for individual circadian phase. This study investigated the feasibility of exploring the hypothesis that an individual’s circadian phase at the time of vaccination is related to antibody response rather than time of day alone.Methods: Twenty healthy adults (aged 20–28) underwent continuous wrist actigraphy monitoring for 14 days using the Corsano Cardiowatch 287-2B. Participants were randomized to morning (08:00–09:00 am) or afternoon (4:00–5:00 pm) influenza vaccination times. Circadian profiles were constructed using cosinor modeling of biomarkers. Hemagglutination inhibition assays quantified H1N1 and H3N2 antibody titers at baseline and 30 days post-vaccination. Regression analyses evaluated associations between circadian phase at the time of vaccination and antibody response.Results: Cortisol peak phase difference at time of vaccination had a positive association with antibody magnitude for both H1N1 and H3N2 strains (H1N1: R2=0.516, p=0.001; H3N2: R2=0.344, p= 0.012). Heart rate variability (HRV) trough phase difference at the time of vaccination had a negative association with antibody magnitude for H1N1 and H3N2 strains (H1N1: R2=0.636, p=0.001; H3N2: R2=0.616, p=0.001). No significant differences were found in antibody magnitude between morning and afternoon vaccination groups.Conclusion: Circadian phase of cortisol and HRV, estimated using wrist actigraphy, may be associated with differences in antibody response to the influenza vaccine. These preliminary findings support further investigation into the relationship between individual circadian timing and adaptive immune function.