Epigenetic profiles of mouse splenic macrophages responding to a Protein-Free Vaccine that Induces Trained Immunity and Protects against Nosocomial Pathogens

Traditional vaccines are difficult to deploy against the diverse antibiotic-resistant, nosocomial pathogens that cause Hospital Acquired Infections (HAIs). We developed a unique, protein-free vaccine to present antibiotic-resistant HAIs. This vaccine protected mice from invasive infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, multidrug resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Rhizopus delemar, and Candida albicans. Protection persisted even in neutropenic mice infected with A. baumannii or R. delemar. Protection was already apparent after 24 hours and lasted for up to 21 days after a single dose, with a second dose restoring efficacy. Protection persisted without lymphocytes but was abrogated with macrophages depletion. This vaccine induced trained immunity by altering the macrophage epigenetic landscape and the inflammatory response to infection. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modification H3K27ac from mouse splenic f4/80+ macrophages extracted from Naïve (non vaccinated) mice, and vaccinated mice at 3 days and 21 days following vaccination.