Impact of Metformin on Immunity

The objective of this study is to determine whether metformin (MET) can improve the immune response to the pneumococcal conjugate vaccine (PCV-13) in older adults, and if this effect is mediated by the gut microbiota. The proposed research projects will provide the necessary pilot data for future, more definitive, studies that will evaluate the impact of immunomodulatory therapies, such as MET therapy, on the aging immune system. The specific aims are: Aim 1. Compare PCV13 vaccine response in elderly adults (≥63 years of age) treated with MET vs. placebo. For this study, 50 elderly volunteers will be enrolled and randomly assigned to receive MET or placebo. The hypothesis that MET can improve vaccine responsiveness by measuring serotype-specific IgG concentrations before and 30 days after PCV13 administration will be tested. Aim 2. Determine whether the frequencies of immunophenotypes differ between elderly adults treated with MET vs. placebo. The mechanisms of MET's effect on the immune system by comparing immunophenotypes of MET and placebo groups between baseline and prior to PCV13 and between baseline and 30 days after PCV13 administration will be explored.