Scientists have developed a new method of boosting
the ageing immune system using a naturally occurring
chemical compound called spermidine. Early tests in
mice, published in the journal eLifeopens show that
the compound restores the immune system’s inbuilt
‘memory’ enabling it to mount a more powerful
protective response following vaccination.
The compound is now being developed by the
researchers as a potential drug to make vaccines
more effective in the elderly, which in future could
help protect this vulnerable population from
seasonal flu and other infections.
Spermidine is a naturally occurring chemical that is
produced within the body. It is also found in a
large number of foods, including cheese, mushrooms,
soy and whole grains.
Professor Katja Simon, senior author of the study,
from the Medical Research Council (MRC) Human
Immunology Unitopens in new window at Oxford
Universityopens in new window, said:
'Viral infections like flu are unpleasant for most
people, but can be very serious for the over-65s and
vaccines, like the free annual flu jab, are the best
form of protection. Our aim is to make that
protection even better, by adding immune boosting
compounds to routine vaccinations.'
The elderly population, in particular people over
65, don’t always get adequate protection from the
flu jab. This is because as we age, our immune
system becomes less effective at responding to new
infections, and even to ones we’ve had in the past.
The reasons for this decline in immunity are
complex, but a key factor is that the white blood
cells that coordinate the response to an infection –
called T cells – lose the ability to form a ‘memory’
of the infection. Therefore when elderly people
encounter a virus, even if it’s one they’ve had
before or have been vaccinated against, they are
unable to mount a strong immune response and can
develop a serious, even fatal, infection.
Researchers have now identified a key cellular
process that is essential for the formation of
immune memory and show that this process becomes
defective in immune cells with age, helping to
explain why immunity diminishes over time. By
targeting this process with spermidine, the
scientists managed to improve the ageing immune
system’s ability to respond to the flu vaccine.
Spermidine works by enhancing a normal cellular
process called autophagy, where parts of the cell
that have become defective or damaged are broken
down and destroyed within cell.
The researchers found that mice lacking a gene
important for autophagy couldn’t make memory T cells
when given the flu vaccine. They also saw that
levels of autophagy were lowered in T cells from
aged mice, suggesting that autophagy is a vital part
of forming the immune memory into old age.
When aged mice were given spermidine prior to flu
vaccination, their T cell response was enhanced
dramatically. The researchers have patented
spermidine and will now see if they can use the
compound, or other autophagy-enhancing drugs, to
improve responses to already licensed vaccines in
mice before hopefully moving on to early safety
trials in humans.
For more information
Autophagy is a critical regulator of CD8+ T cell
memory formation.
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