The effects of metformin on influenza vaccination responses in healthy older adults

Abstract With aging, there is a progressive decline in the immune system leading to increased risk of infection and diminished vaccination responses. Concurrently, there are age-related changes to systemic and cellular metabolism. Influenza (flu) is a leading killer of older adults despite availability of a seasonal vaccine. Metabolic adjuvants may target metabolic deficits in immune cells and have potential to increase vaccination efficacy. Here we aimed to determine the effects of metformin, an FDA approved diabetes drug that targets AMPK and modulates cellular metabolism, on flu vaccination responses. In this study, healthy older adults (non-diabetic/non-prediabetic, age: 74.4±1.7 years) were randomized to metformin (n=8, 1500mg XR/daily) or placebo (n=7) treatment for 20 weeks. 10 weeks after the start of treatment, subjects were vaccinated with High Dose Flu Vaccine. Blood was obtained prior to treatment, prior to vaccination, and 1, 5, and 10 weeks post vaccination. To evaluate the effect of metformin treatment on vaccination responses, peripheral blood mononuclear cells (PBMCs), serum, and plasma were collected from each visit. Serum antibodies titers were quantified and PBMCs were stimulated with live flu virus to assess cell-mediated responses. Clear responses to vaccination were seen in T and B cell subsets via flow cytometry. There were trending increases in antibody fold changes with metformin, indicating a need to further explore the effects of metformin on humoral responses. Overall, metformin had no negative effects, but requires additional studies to determine if it has favorable effects on flu vaccine responses in healthy older adults. Supported by American Federation for Aging Research (AFAR Diamond 18155, Bartley) and J. Bartley start up funds