Improving vaccination in older adults by inducing autophagy with spermidine

Co-Investigators: Paul Klenerman, University of Oxford

The immune system becomes less efficient with age. Immune cells perform less well and decrease in numbers. Ageing leads to excess inflammation that can blunt immune responses and make age-related diseases such as cardiovascular and heart diseases worse. Immune ageing can also lead to the wrong type of immune response, such as seen in older patients with COVID-19 and to reduced vaccination efficacy, for example in vaccination against flu.

Autophagy is a key way for cells to degrade and recycle debris and malfunctioning organelles. We have shown that autophagy is reduced with age in immune cells. We found a natural way to turn autophagy on with spermidine, a food supplement, improving vaccination efficacy in preclinical models. We have discovered the molecular pathway Improving vaccination in older adults by inducing autophagy with spermidine downstream of spermidine. Spermidine is safe, available from health retailers, and has been trialled showing that it improves cognitive function.

Here we are conducting a clinical trial in 120 in older adults to test if spermidine improves vaccination responses against SARS-CoV2 and influenza in collaboration with the Oxford Vaccine Group.

This is the first time that the effect of spermidine on the immune system is being tested in humans. This study is also a unique way to understand spermidine’s effect on human cells as unlike cells from any other tissue, immune cells are available from the volunteer’s blood. Lastly, we hope to confirm and find more specific drug targets along the novel autophagy pathway that will improve ageing of the human immune system and other tissues.