Interplay between circadian clock and viral infection
OBJECTIVES Older adults are less able to produce a protective antibody response to vaccinations. One factor that contributes to this is immune ageing. Here we examined whether diurnal variations in immune responses might extend to the antibody response to vaccination. DESIGN We utilised a cluster-randomised trial design. SETTING 24 General Practices (GPs) across the West Midlands, UK who were assigned to morning (9-11am; 15 surgeries) or afternoon (3-5pm; 9 surgeries) vaccination times for the annual UK influenza vaccination programme. PARTICIPANTS 276 adults (aged 65+ years and without a current infection or immune disorder or taking immunosuppressant medication). INTERVENTIONS Participants were vaccinated in the morning or afternoon between 2011 and 2013. MAIN OUTCOME MEASURES The primary outcome was the change in antibody titres to the three vaccine influenza strains from pre-vaccination to one month post-vaccination. Secondary outcomes of serum cytokines and steroid hormone concentrations were analysed at baseline to identify relationships with antibody responses. RESULTS The increase in antibody levels due to vaccination differed between morning and afternoon administration; mean difference (95% CI) for H1N1 A-strain, 293.3 (30.97-555.66) p=.03, B-strain, 15.89 (3.42-28.36) p=.01, but not H3N2 A-strain, 47.0 (-52.43 to 146.46) p=.35; those vaccinated in the morning had a greater antibody response. Cytokines and steroid hormones were not related to antibody responses. No adverse events were reported. CONCLUSIONS This simple manipulation in the timing of vaccine administration to favour morning vaccination may be beneficial for the influenza antibody response in older adults, with potential implications for vaccination strategies generally. TRIAL REGISTRATION This trial is registered with the ISRCTN (ISRCTN70898162).