Research published in Nature Communications in December 2022 suggests that vaccination at different stages of a mouse’s circadian rhythm has different effects. This could be used to shape future vaccination schedules in order to initiate greater immune responses. Researchers from the Royal College of Surgeons in Ireland University of Medicine and Health Sciences investigated the effect that circadian rhythms have on Dendric Cell (DC) function and whether it might “explain the diurnal variability observed in the protective immune response induced by certain vaccines”.  

What do we know already? 

The study introduces the “critical role” of DCs in “priming adaptive immune responses” to infection or vaccination. They also “express all the components of the endogenous molecular clock and display circadian rhythmicity in gene expression”.  

“These cellular timers produce daily oscillations in a range of critical immune cell functions, such as phagocytosis, cytokine production, cell trafficking, cell migration, along with anti-parasite, antibacterial, and antiviral immune responses.”

The authors suggest that, despite the knowledge that vaccination in the morning has demonstrated stronger responses than vaccination in the afternoon or evening, the “mechanisms modulating these time-of-day differences” are “poorly understood”. Therefore, they set out to investigate the effect of circadian rhythms on DC function, and whether “this might explain the diurnal variability observed in the protective immune response induced by certain vaccines”.  

What did they learn? 

The “significant finding” of the study is that the molecular clock in DCs “influences T cell responses”. The authors state that the molecular clock demonstrably “orchestrates a series of events” such as “altering mitochondrial morphology” and “coordinating calcium localisation to regulate antigen processing and presentation”. 

“Daily oscillations in mitochondrial morphology and its associated metabolic output impact on the capacity of DC to process and present antigens to T cells.” 

The research offers insights into the effects of circadian rhythms on antigen processing, which the authors hope “could inform the develop of chronotherapeutic vaccination strategies”.  

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