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Nature Sci Reports: The effect of the time of day of influenza vaccination on antibody and T-cell responses in older adults

Michael Coston

Editor, Senior Moderator

Nature Sci Reports: The effect of the time of day of influenza vaccination on antibody and T-cell responses in older adults​


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Photo Credit - CDC PHIL

#19,407

Ten years and just over 8,000 blogs ago, in Vaccine: Taking Your Best Shot, we looked at a study published in the Journal Vaccine which suggested the time of day one is vaccinated may make a difference in the body's immune response.

The cluster-randomized trial followed 276 adults (over 65) across 24 GP practices in the West Midlands, UK who - between 2011 and 2013 - were assigned to receive their flu shots either in the morning or afternoon.

Follow up blood work showed higher antibodies against H1N1 and Influenza B (but not H3N2) in the morning vaccination cohort. (note: a follow-up Corrigendum - published several months later - weakened the evidence, finding that the influenza B result was no longer statistically significant).

Last week, a new study published in Nature Scientific Reports, revisits the idea and reports:

Individuals vaccinated in the early morning (09:00) showed an approximately 32% stronger antibody response compared to individuals vaccinated in the afternoon (14:00)
That said, their results were mixed. Their main analysis found no statistically significant differences between vaccination periods, but a secondary analysis favored morning vaccination over early afternoon.

But curiously, not over late afternoon.
Whether this effect actually results in improved vaccine protection hasn't been established, and the reasons behind the purported `afternoon trough' - assuming it is more than just a statistical variation - remains unclear.

It is possible our internal body clocks may play a role. Some people (like myself) are early risers, so the same appointment time may fall at different points in our `biological day'.
The researchers explored that possibility using patient's sleep schedules, but those results were inconclusive as well.

Make of it what you will.
I've posted the abstract and a snippet from the discussion. Follow the link to read the study in its entirety.


The effect of the time of day of influenza vaccination on antibody and T-cell responses in older adults

Published: 05 November 2026

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Tamara M. J. Brouwers, Koen Vink, Martijn Vos, Harry van Dijken, Marijn E. Snik, Jan van de Kassteele, Lisa Beckers, Debbie Smit, Deborah Oomen, Teun Guichelaar, Tobias N. Bonten, Laura Kervezee, Jacco Wallinga & Debbie van Baarle

Abstract

Increasing evidence suggests that time of day of vaccine administration affects immune responses
. We aimed to determine the optimal time of day for influenza vaccination by characterising temporal patterns in vaccine-induced immune responses. Additionally, we assessed the effect of vaccination time relative to an individual’s circadian phase on immune responses.

A randomised controlled trial was conducted with 278 participants aged 60–85 years, who received influenza vaccination at a randomised time between 09:00 and 17:00.
Antigen-specific antibody titers and T-cell responses to three vaccine strains (A/H1N1, A/H3N2 and B/Victoria) were measured pre- and one month post-vaccination. A permutation-based test was used to determine differences in strain-specific immune responses between the three randomisation time blocks (09:00–11:40, 11:40–14:20, 14:20–17:00).

As a secondary analysis, strain-specific immune responses were jointly analysed in a single generalised additive mixed-effects model (GAMM) to assess the overall impact of influenza vaccination timing. The permutation-based test found no significant differences in immune responses between the three vaccination time blocks. A GAMM revealed that morning vaccination resulted in significantly higher antibody responses across strains than early afternoon vaccination(p = 0.045), but not late afternoon vaccination (p = 0.498).

Antibody responses displayed a non-significant non-linear pattern from 09:00 to 17:00, with the model suggesting highest responses in participants vaccinated at 09:00. A similar trend was observed for T-cell responses.

Irrespective of chronotype, vaccinations administered at the start of an individual’s day tended to elicit the strongest vaccine-induced immune responses. Although statistical evidence for a time-of-day effect was limited, numerically higher antibody and T-cell responses were consistently observed in the morning group.
(SNIP)

Discussion

This study showed a consistent trend toward stronger strain-specific antibody and T-cell responses among older adults vaccinated in the morning compared to those vaccinated in the afternoon. However, the differences between vaccination time groups did not reach statistical significance in our primary analysis. After adjustment for variation in baseline antibody titers using GAMM analyses, overall antibody responses differed significantly between the morning and early afternoon vaccination groups, but not between the morning and late afternoon vaccination groups. An important strength of the study is its assessment of temporal patterns in vaccine-induced immune responses across a continuous vaccination window from 09:00 to 17:00. A trend was observed toward stronger vaccine-induced immune responses following vaccination in the early morning (at 09:00).
(SNIP)

In conclusion, we consistently showed that morning influenza vaccination tended to result in stronger vaccine induced immune responses than (early) afternoon vaccination in adults aged 60–85 years. Our results contribute to the growing evidence on the effect of vaccination timing on vaccine-induced immune responses and suggest potential clinical relevance in older adults. Optimising the timing of vaccine administration may therefore offer a safe and cost-effective strategy to enhance immunogenicity of current influenza vaccines, although further investigation into clinical outcomes is warranted.
(Continue . . . )



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