title: Morning vaccination enhances antibody response over afternoon vaccination: A cluster-randomised trial.
abstract: 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.
  
  
  
  We utilised a cluster-randomised trial design.
  
  
  
  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.
  
  
  
  276 adults (aged 65+ years and without a current infection or immune disorder or taking immunosuppressant medication).
  
  
  
  Participants were vaccinated in the morning or afternoon between 2011 and 2013.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  This trial is registered with the ISRCTN (ISRCTN70898162).
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Long
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Taylor
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Kai M
authors.initials: KM
authors.lastname: Toellner
authors.affiliation: Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Lord
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: a.c.phillips@bham.ac.uk.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Phillips
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D013997:Time Factors; D014611:Vaccination / Q000379:methods*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: Ageing; Antibodies; Cluster-randomised; Influenza vaccine; Time of day; Vaccination