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In recent years, many of us will have had extra vaccines. But could the time of your vaccine appointment affect your body’s response to it? A new SFI-funded project called ChronoVac is exploring the frontier field of how the immune system can respond differently to threats and stimulants at different times of the day and night, with a view to designing a vaccine that can optimise the kind of immune response you want to see.

Our body clocks tune up and down many functions in our bodies, explains Dr Annie Curtis, who leads the Curtis Clock Lab at RCSI. “We really are 24-hour time machines, and the more we look the more we see that our body clocks control many aspects of our biology,” she says. “And there have been some recent studies that showed that people had different responses to flu and BCG vaccines depending on the time of day when they received them, but these were observations, little has been explored about how this was happening.”

Professor Curtis thought these findings about immune responses to vaccines were ‘interesting’ but it was when one of the researchers in her lab showed her a particular finding, it stopped her in her tracks. “Dr Mariana Cervantes-Silva found there was a time-based change in a type of immune cell called a dendritic cell in mice,” she recalls.

Image of small glass vials, containing clear liquid; a clock; and a syringe
“You could see that depending on the time of day, little components within these cells called mitochondria had completely different shapes. At one time of day the mitochondria were all joined together like a string of beads, and at another time of day they were completely separate. That just blew my mind.”

What has this to do with the immune system? Mitochondria are like the powerhouses of our cells, they are the site where energy is generated, but they also play an important role in processing ‘foreign’ molecules so they can be interpreted by the immune system, explains Professor Curtis.

“We know that when you deliver a vaccine, dendritic cells pick up the vaccine and chop it up it so it can be presented to the immune system, and Dr Richard Caroll - the other lead author of this study - clearly showed that mitochondria are involved in this process,” she says. “So now we were asking ourselves if these time-based changes in the mitochondria could be related to the different responses we see when vaccines are given at different times.”

The mouse mitochondria findings, which were published in Nature Communications in 2022, sparked the development of ChronoVac, a new project funded under the SFI Frontiers for the Future programme and led by RCSI. The idea is to understand and make use of how the body-clock affects  immune response to vaccines.

“We want to understand more about how dendritic cells in the skin respond to vaccines such as the flu vaccine and how the time of administration affects that, and also how we could use painless microneedles to target the vaccines to the dendritic cells,” says Dr Curtis, who is collaborating on the project with microneedle expert Professor Ryan Donnelly at Queen’s University Belfast.

“Initially, a body-clock optimised vaccine may be of particular benefit to groups such as older people, who typically have a lower immune response that we want to boost,” she adds. “But thanks to COVID-19, the whole field of mRNA vaccines has exploded and I think in decades to come we will have new vaccines for all sorts of conditions. If we know how to tune the vaccines to work with the body clock, then that will be of enormous value in getting the optimal immune response.”