Authors: Brady RA, Leid JG, Costerton JW, Shirtliff ME
Title: A Quadrivalent Vaccine Protective Against Chronic Osteomyelitis Due To Staphylococcus Aureus Biofilms
Institution: University of Maryland - Baltimore Dental School, Baltimore MD
Purpose: Staphylococcus aureus is a leading cause of nosocomial infections. Half of these illnesses are caused by the multi-drug resistant methicillin-resistant S. aureus (MRSA), and community-acquired MRSA infection is becoming increasingly common.
Methods: In previous work we identified 22 cell wall-associated immunogens, of which several were up-regulated during biofilm growth. We hypothesized that these antigens, when administered as a vaccine, could decrease infection levels in a rabbit model of S. aureus tibial osteomyelitis. Four candidate antigens were chosen, and purified, recombinant forms of each were generated. These recombinant proteins were combined into a multi-component vaccine with adjuvant and administered to New Zealand White rabbits, with a second vaccination given ten days later. Ten days following the boost, the animals were challenged through percutaneous inoculation of the left tibia with MRSA. After a further ten days, vancomycin was administered to both a vaccinated and a non-vaccinated group. Two weeks after challenge, vaccine and antibiotic efficacy were assessed through evaluation of clinical, radiological and bacteriological signs of infection.
Results: Compared to a non-vaccinated and untreated control group, vaccinated animals and animals treated with vancomycin alone showed no significant differences. However, those animals who were both vaccinated and treated with vancomycin showed significant decreases in tibial bacterial load (P = 0.025), proportion of animals infected (P = 0.03) and clinical (P = 0.009) and radiological (P = 0.00025) signs of infection.
Discussion and Conclusion: Therefore, this vaccine-when used in conjunction with antibiotic treatment-was able to significantly abrogate the clinical and radiological signs of osteomyelitis in a rabbit model of disease and greatly diminish S. aureus colony counts in the infected bone. We hypothesize that whilst the vaccine was able to prevent biofilm formation, its use selects for planktonic survivors. The opposite was true in animals treated only with antibiotics. Thus the combination of vaccine and antibiotic was able to clear the infection completely.