Old epilepsy drug repurposed as a low-cost metabolic vaccine booster increases T-cell responses 10-fold in a human trial

Summary A multiomic screen matched T-cell memory transcriptional signatures against >30,000 drug perturbation profiles, identifying lysine deacetylase inhibitors (KDACi) as candidate immunometabolic adjuvants. Low-dose sodium valproate enhanced glutaminolysis-dependent memory precursor (IL7Rhi PD1lo) differentiation in primary human CD8+ T cells and boosted memory responses across four murine infection/immunization models. In a randomized experimental study with humans (MEMRI, n=69 HLA-A*02:01+ adults) receiving seasonal trivalent influenza vaccine, 7-day oral valproate produced a >10-fold increase in influenza-specific CD8+ T-cell counts and a >2-fold increase in vaccine-strain IgG/IgA titers versus controls, with expanded cross-strain antibody breadth and no increase in adverse events. Comment: For a clinician like myself, this is a difficult manuscript to read and understand, and admittedly, I can only hope I got the above summary and message right. This is an “old drug repurposing” story, supported by in vitro, animal, and human data. In 69 young, healthy, HLA-restricted volunteers, the above-described T-cell response-enhancing effect was...