Repurposed epilepsy drug could be used to boost vaccine protection among elderly

A Cambridge-led team showed that the drug more than doubled the number of antibodies against flu and increased 10‑fold the number of flu-specific CD8 T cells, a type of white blood cell that kills cells infected by flu.

Vaccination helps protect individuals from infection by priming the immune system to recognise and attack invading pathogens, such as viruses and bacteria. But for people with weaker immune systems, vaccines do not always offer strong or lasting protection, often requiring multiple ‘booster’ shots to maintain immunity. 

Enhancing the immune system’s ‘memory’ – helping ensure it is able to recognise and respond to target pathogens for longer – could be a way to increase vaccine efficacy. Greater memory responses are associated with reduced infections and, for those who do get infected, less severe illness. 

A common way to boost immune memory is through the use of adjuvants, vaccine components that aim to enhance the size, breadth and durability of a vaccine response. 

In recent years, scientists have begun exploring whether drugs that have already been shown in clinical trials to be safe can be repurposed to treat other conditions. In research published in Nature Communications, scientists at the University of Cambridge explored whether existing drugs might be repurposed as adjuvants, particularly for people with weaker immune systems.

Professor Eoin McKinney from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, who led the research, said: “Vaccines protect us by teaching our immune systems to remember viruses or bacteria so we can respond quickly if we’re exposed to them again. For many people, though, vaccines don’t work as well as we’d like, so we need to find ways to boost their effectiveness safely.”

The team compared the genetic profile of long‑lived immune memory cells against data showing how human cells change their gene activity when exposed to over 30,000 different drugs and chemicals. They found that a class of drugs known as lysine deacetylase inhibitors make cells behave, at a genetic level, like immune memory cells. 

The researchers then took immune cells known as T cells, extracted from blood donations from healthy volunteers, and reprogrammed them to behave as if exposed to a virus or vaccine. They treated these cells to low doses of the shortlisted drugs and watched how the cells changed over several days.

One drug in particular, delivered at very low doses, stood out: sodium valproate, a drug used in much higher doses to treat conditions such as epilepsy. It appeared to ‘programme’ the immune cells’ memory by adjusting epigenetic modifiers – ‘switches’ that turn up or down activity of the cell’s DNA.

Mice exposed to influenza and/or Covid-19 vaccination alongside being given sodium valproate showed stronger immune responses and recovered faster than those mice not given the drug.

Finally, the team carried out a controlled human vaccination study in 74 healthy adults, all of whom were given the seasonal flu vaccine. The volunteers were randomised into one of three groups: one group was also given sodium valproate at a 5% dose compared to typical epilepsy treatment over seven days; the second was given a 10% dose of the drug over the same period; and a third group was given only the vaccine.

Compared to individuals given only the flu vaccine, those treated with sodium valproate were found to have double the number of flu-specific antibodies and 10 times as many flu-specific T‑cell responses, with none of the side-effects commonly seen in patients treated with much higher doses. They also showed a wider breadth of antibody responses, meaning they would be better protected against virus variants.

Joint first author Dr John Sowerby, also from CITIID, said: “We’ve shown that a commonly-prescribed drug, sodium valproate – usually used to treat epilepsy – can act as a new type of vaccine booster. It does this by rewiring how key immune cells work, helping them develop into memory precursor cells, which stick around long-term after vaccination.”

Sodium valproate is already licensed worldwide and is inexpensive. At high doses, it can carry a risk of birth defects if taken during pregnancy, and other side-effects such as nausea, weight gain and headaches. However, this new study shows that the drug can be an effective adjuvant even at very low doses, where side-effects are likely to be relatively insignificant. 

The researchers now plan to test this approach in older patients to see if the drug can boost their immune memory responses. If successful, it could lead to larger clinical trials to assess its efficacy.

Dr Prasanti Kotagiri, joint first author, who carried out the work while at CITIID, said: “Sodium valproate could dramatically improve vaccine protection in groups who need it most, such as older adults. Because it would be given in much lower doses and over a very short amount of time, side-effects would be far less of any issue.”

Professor McKinney added: “The vast majority of drugs fail at the clinical trial stage, but this is a drug for which we already have decades of data on and know its safety profile, meaning it could be developed as an adjuvant much faster than if we were starting from scratch.”

The research was mainly funded by the Wellcome Trust and Beit Trust, with additional support from the National Institute for Health and Care Research Biomedical Research Centre.

Reference

Sowerby, JM et al. Multiomic analysis identifies glutaminolysis-1 dependent metabolic enhancement of immune memory utilised for vaccine development. Nat Comms; 26 Jun 2026; DOI: 10.1038/s41467-026-74866-4