Epilepsy drug sodium valproate could improve vaccine immune responses

A widely used epilepsy drug could significantly improve the effectiveness of vaccines, offering greater protection for older people and those with weakened immune systems, according to new research led by the University of Cambridge.

Scientists found that sodium valproate, when given in very low doses alongside a seasonal flu vaccine, more than doubled the number of flu-specific antibodies and increased flu-specific CD8 T cells tenfold. The findings suggest the drug could be repurposed as a vaccine booster, strengthening the body’s long-term immune response.

Boosting immune memory

Vaccines work by training the immune system to recognise viruses and bacteria, enabling it to respond more quickly if exposed in future. However, immune responses can weaken with age or illness, meaning some people require repeated booster vaccinations to maintain protection.

Researchers believe strengthening the immune system’s memory could improve vaccine performance and provide longer-lasting immunity.

Vaccines work by training the immune system to recognise viruses and bacteria, enabling it to respond more quickly if exposed in future

“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,” said Professor Eoin McKinney from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the University of Cambridge, who led the research.

The team compared the genetic characteristics of long-lived immune memory cells with data from more than 30,000 drugs and chemicals, identifying a class of compounds known as lysine deacetylase inhibitors as potential candidates for enhancing immune memory.

Promising trial results

Laboratory tests showed that sodium valproate, commonly prescribed in much higher doses to treat epilepsy, could reprogramme immune cells by altering epigenetic switches that regulate DNA activity.

Experiments in mice vaccinated against influenza or COVID-19 demonstrated stronger immune responses and faster recovery when the drug was administered alongside vaccination.

Researchers then carried out a controlled study involving 74 healthy adults receiving the seasonal flu vaccine. Participants were randomly assigned to receive either the vaccine alone or the vaccine plus a low dose of sodium valproate over seven days.

Experiments in mice vaccinated against influenza or COVID-19 demonstrated stronger immune responses and faster recovery when the drug was administered alongside vaccination

Those given sodium valproate developed more than twice the number of flu-specific antibodies and ten times as many flu-specific T-cell responses compared with those who received only the vaccine. They also produced a broader range of antibodies, potentially offering greater protection against different virus variants, without experiencing the side-effects typically associated with higher doses of the drug.

“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,” said joint first author Dr John Sowerby, also from CITIID.

Next step for clinical trials

Although sodium valproate can cause side-effects, including birth defects if taken during pregnancy and nausea, weight gain and headaches at higher doses, researchers say the much lower doses used in the study are likely to minimise these risks.

The team now plans to investigate whether the approach can improve vaccine responses in older adults before progressing to larger clinical trials.

“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,” said Dr Prasanti Kotagiri, joint first author.

Sodium valproate could dramatically improve vaccine protection in groups who need it most, such as older adults

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.”