New drug could make vaccines more effective in the elderly
Spermidine enhances the normal cellular process of autophagy
Scientists have developed a new method of boosting the ageing immune system using a naturally occurring chemical compound. Early tests in mice, published in the journal eLife, show that the compound restores the immune system’s inbuilt ‘memory’ enabling it to mount a more powerful protective response following vaccination.
The compound, called spermidine, 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 population from seasonal flu and other infections.
Professor Katja Simon, senior author of the study, from the Medical Research Council (MRC) Human Immunology Unit at Oxford University, said: 'Viral infections like flu are unpleasant for most people, but can be very serious for the over-65s and vaccines, such as 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, in particular people over 65, do not 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 that we have already had.
Our aim is to make protection from viral infections even better, by adding immune boosting compounds to routine vaccinations
A key factor for this decline in immunity 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 is one they have had before or have been vaccinated against, they are unable to mount a strong immune response and can develop a serious, sometimes 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.
First author of the study Daniel Puleston, a PhD student from the MRC Human Immunology Unit at Oxford University, said: 'We already know that the over 65s have a problem forming an immune memory and as a consequence infection causes proportionally more deaths in this age group. We’ve now identified a key process involved in this memory formation, and by enhancing this process in aged mice we’ve been able to boost their immune response to vaccination.
'The effect was so powerful that the treated mice mounted an even stronger T cell response to the vaccine than young mice. It’s the equivalent of a 90-year-old responding to a vaccine better than a 20-year-old, which makes this a very exciting pathway to target as a potential way of boosting vaccine protection in the elderly.'
Spermidine works by enhancing the normal cellular process of autophagy
Spermidine works by enhancing the normal cellular process of 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 could not 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.
Spermidine is not expected to reach the clinic for another 5–10 years.
The research was funded by the MRC and the Wellcome Trust.
