Project Grant R43AI174497

DEVELOPMENT OF A STAPH AUREUS VACCINE - ABSTRACT METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IS OFTEN CONSIDERED THE PROTOTYPE HOSPITAL-ACQUIRED INFECTION. IN SPITE OF THE BILLIONS OF DOLLARS SPENT ON PREVENTIVE MEASURES, ESTIMATES OF THE INCIDENCE ARE IN THE HUNDREDS OF THOUSANDS, WITH TENS OF THOUSANDS OF PEOPLE PER YEAR SUCCUMBING TO DISEASE IN THE USA ALONE. PROPHYLACTIC VACCINES AGAINST S. AUREUS WOULD HAVE AN ENORMOUS IMPACT IN THE HEALTHCARE FIGHT AGAINST ANTIBIOTIC-RESISTANT STRAINS. IN OUR PREVIOUS STUDIES, WE USED A NOVEL METHOD TO GENERATE NEXT-GENERATION WHOLE-CELL STAPHYLOCOCCUS VACCINE CANDIDATES THAT RESULTED IN HIGH LEVELS OF CLEARANCE IN A STRINGENT BIOFILM MODEL OF INFECTION. THE METHOD UTILIZES A MANGANESE-DECAPEPTIDE-PHOSPHATE (MDP) COMPLEX THAT HAS BEEN ADAPTED FROM THE RADIATION-RESISTANT BACTERIUM, DEINOCOCCUS RADIODURANS. WE PROPOSE TO FURTHER DEVELOP THIS APPROACH BY DIRECTLY COMPARING SEVERAL OF THE IDENTIFIED VACCINE CANDIDATES AND NEXT-GENERATION MODIFIED VERSIONS IN EXPANDED STUDIES. CANDIDATES WILL BE TESTED FOR STIMULATING PROTECTIVE IMMUNITY IN BIOFILM PIN IMPLANTATION AND ABSCESS MOUSE MODELS. DOWN- SELECTED "BEST" CANDIDATES WILL ALSO BE TESTED IN A S. AUREUS PREEXPOSURE MODEL AS DIFFERENT IMMUNOGENS (PROTEIN SETS) CIRCUMVENT DECEPTIVE IMMUNE IMPRINTING. THESE EXPERIMENTS SHOULD ALLOW US TO CATEGORICALLY REPORT WHICH CANDIDATE PROVES THE MOST EFFICACIOUS IN RELEVANT ANIMAL MODELS, AND POSITION A CANDIDATE READY FOR CROSS- PROTECTION, DOSING, AND TOXICITY STUDIES TO FOLLOW.