Trained Immunity based vaccine

Traditional vaccines provide pathogen-specific protection, and are thus difficult to deploy against the diverse antibiotic-resistant, nosocomial pathogens that cause Hospital Acquired Infections (HAIs). We discovered a unique, protein-free vaccine that protected mice from invasive infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, and Candida albicans. Protection persisted even in neutropenic mice infected with A. baumannii or mucormycosis. Protection began by 24 hours after administration, and lasted for up to 21 days after a single dose, with a second dose restoring efficacy. Protection persisted despite absence of lymphocytes but was abrogated by depletion of macrophages, and the vaccine altered macrophage epigenetics and inflammatory response to infection, consistent with trained immunity. Given typical durations of acute hospitalizations, this short-term protection against lethal infection caused by diverse bacterial and fungal pathogens suggests this vaccine is a promising means to prevent antibiotic-resistant HAIs.