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expert reaction to study investigating morning versus afternoon flu vaccine administration and vaccine effectiveness

Vaccines are used to offer protection against a number of diseases and so ensuring their effectiveness is important, and a study published in the journal Vaccine has reported that flu vaccines given in the morning brought about a greater immune (measured by antibody levels) response than those given in the afternoon.


Dr Ben Neuman, Lecturer in Virology, University of Reading, said:

“I think the most important message to take away from this study is that vaccinations work, no matter what time of day they are given.

“It takes around a month after vaccination for the body to make a mature antibody response. In that month, there are millions of chance encounters between cells of the immune system and the vaccine, and then a period where many times as many cells randomly stitch and mutate bits of DNA in an attempt to build working antibodies. The idea that a six-hour delay in the start of the month-long, mostly random process of making antibodies could make any meaningful difference to the outcome doesn’t make much sense to me.

“What I think happened is that, despite following what appeared to be a reasonable experimental design, there was enough of a difference between the people in the morning vaccine group and the afternoon vaccine group to skew the results.”


Dr Rachel Edgar, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, said:

“This robust study shows that our antibody responses to seasonal flu vaccines depend on the time of day at which they are given, and suggests vaccines may be more effective when administered in the morning, rather than afternoon. Further investigation is required to determine if morning vaccination strategies reduce the incidence of disease, and how vaccine efficacy is governed by our circadian (24h) rhythms.

“Individual cells in the body are able to keep track of time using their biological clocks, including immune cells that respond to infectious diseases. Currently we know very little about how our circadian clocks interact with viruses at the molecular level. The preliminary findings in this paper highlight the potential health and economic benefits we could glean from understanding the interaction between circadian rhythms and flu.”


Prof. Adam Finn, Professor of Paediatrics, University of Bristol, said:

“The results are interesting but it should be emphasised that the clinical importance of the findings is not clear at this point – this is preliminary research.

“The effect looks stronger for H1N1 but one would also want to look at antibodies by another technique called microneutralisation to get a better feeling for the likely impact on protection.

“It would also be important to assess whether these early results translate into better protection over time.

“The authors are likely to be planning these further studies which would need to be done before making any recommendations to change current practice on timing of vaccinations.

It is possible, for example, that advising that vaccine only be given in the morning might reduce the number of doses given overall and thus reduce protection against flu rather than increase it.”


Prof. Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“We know that a variety of factors, such as diet, sleep and exercise seem to impact on your immunity, but the fact that the amount of antibody produced following influenza vaccination differed according to whether or not the people included in the study were immunised in the morning or in the afternoon was intriguing.

“But we have to remember – differences in antibody yield that are statistically significant might not be biologically significant, and that’s the key issue. We would need to see whether or not people vaccinated in the afternoon were more likely to become infected by the virus before we could say that timing of immunisation impacts on success.”


Dr Richard Pebody, head of flu surveillance for Public Health England, said:

“This is an interesting study and indicates more research is needed. Flu vaccine is the best protection we have against an unpredictable virus which can cause severe illness and deaths each year among at-risk groups, including older people, pregnant women and those with a health condition, even one that is well managed.”


‘Morning vaccination enhances antibody response over afternoon vaccination: A cluster-randomised trial’ by Joanna E. Long et al. published in Vaccine on Tuesday 26 April 2016.


Declared interests

Dr Ben Neuman: “No conflicts of interest.”

Dr Rachel Edgar: “I have no conflicting interests. My research is focused on the molecular interaction between viruses and circadian rhythms.”

Prof. Adam Finn: “No conflicts to declare.”

Prof. Jonathan Ball: “No conflicts of interest.”

No others received.

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