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New drug could make flu vaccines more effective in the elderly (2014-11-28)

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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