Older adults who receive their influenza vaccinations in the morning may be better protected, according to results of a UK study.

Four weeks postvaccination, the antibody levels to two of the three influenza strains in the trivalent vaccine were higher in individuals who received their influenza vaccination in the morning compared to those who received their vaccination in the afternoon (mean difference of 293.3, 95 percent CI, 30.97-555.66; p=0.03 for H1N1 A-strain and 15.89, 95 percent CI, 3.42-28.36; p=0.01 for H1N1 B-strain). There was no difference demonstrated with the H3N2 A-strain (mean difference of 47.0, 95 percent CI, -52.43-146.46; p=0.35). [Vaccines 2016;doi:10.1016/j.vaccine.2016.04.032]

Cytokine and steroid hormone levels (measured to determine potential mechanism behind impact of time of day and/or gender on response to vaccination) did not appear to affect antibody levels, and there were no serious adverse events reported.

“Adjusting the timing of vaccination may be a simple, cost neutral and effective public health intervention to improve vaccination responses, particularly in older adults,” said the authors, who cautioned that the best time for vaccination may differ between vaccines.

This cluster-randomized trial, conducted between 2011 and 2013, involved 24 general practices, 15 assigned to morning vaccinations (9-11 am) and nine to afternoon vaccinations (3-5 pm) as part of the annual UK influenza vaccination programme. Participants (276 individuals aged ≥65 years who did not have a current infection, immune disorder, cancer, diabetes, or chronic inflammatory disease, and were not on immune-affecting medication) were vaccinated either in the morning or afternoon.

“[While] results showed that antibody responses to two of three influenza strains were higher when the vaccination was given in the morning, whether these differences relate to clinical disease resistance remains to be examined,” said the authors.

According to study author Dr. Anna Phillips, Reader in Behavioural Medicine, School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, UK, the mechanism behind these findings is still unknown.

“We currently don’t know [the mechanism], as we measured all the potential obvious suspects in terms of immunity and hormones and how they interacted together,” said Phillips. “Potentially it is something to do with the number of naive circulating T cells which is higher in the morning that my colleague [Professor Janet Lord, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK] recently found in a small [unpublished] pilot study,” she said.

Phillips also stressed on the necessity of larger studies to confirm these findings. “We need to confirm this in a larger sample with older adults with a whole range of diseases or comorbidities as well as establish whether this links directly to protection against getting [influenza], although that is what antibody levels are meant to translate to. This is yet to be established, which would require a very large sample size.  Also, we would like to extend this to other important vaccinations [such as the pneumonia vaccine], particularly for older people,” she said.

Previous studies have shown that immune system function declines with age, leading to more severe infections and poorer response to vaccines in the older population, which is already one of the most at risk for influenza-related hospitalizations and complications.