Drugs That Rejuvenate The Ageing Immune System Could Improve Covid Vaccine Effectiveness

• The elderly are less responsive to vaccination due to a weakened immune system.
• Inhibition of mTOR, in addition to extending lifespan in animals, can improve immunity in humans and boost the effectiveness of influenza vaccines.
• Drugs that inhibit mTOR should be explored as a means to increase the effectiveness of future COVID-19 vaccines in the elderly.

The best way to fight Covid may be to fight ageing. As COVID-19 primarily kills the elderly, treatments aimed at making the ageing immune system behave more like its younger self may be one of the most effective ways to tackle the disease. The means to put this theory to the test exist, and are worthy of exploration, particularly when it comes to boosting older people’s response to vaccination.

Vaccines, which rely on inducing a robust response from the recipient’s immune system, are less effective in elderly people. However, a new class of drugs called rapalogues could be used to rejuvenate the ageing immune system just prior to immunisation, thereby boosting its effectiveness.

Rapalogues inhibit a molecule called mTOR, which is part of a signalling pathway that plays an important role in the ageing process. Inhibiting mTOR not only extends lifespan in all animals that have been studied, but also appears to have a rejuvenating effect on the ageing immune system, reducing infection rates in the elderly and improving flu vaccine responses by 20%. Furthermore, studies from Wuhan and the United States suggest that diabetics taking metformin, a drug that also targets mTOR, were less likely to die from Covid than diabetics not taking metformin (even when the severity of their diabetes was the same).

Of course, until we have a Covid vaccine, it is impossible to know whether such drugs will boost immunisation. However, it is an enticing possibility that should be investigated in vaccine trials, as it may help solve one of the big challenges of developing a Covid vaccine: that the age group most in need of protection against the virus is also the least responsive to vaccination.