D-073. Protective Vaccine against Chronic Infections Due to Staphylococcus aureus Biofilms

R. A. Brady¹, G. O'May¹, J. G. Leid², J. Costerton³, M. E. Shirtliff¹;
¹Univ. of Maryland, Baltimore, MD, ²Northern Arizona Univ., Flagstaff, AZ, ³Univ. of Southern California, Los Angeles, CA.

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. S. aureus is capable of causing chronic disease through a biofilm mode of growth. While several candidate vaccines have been tested, all have focused solely on prevention of acute disease caused by S. aureus in its planktonic form. 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 biofilm infection levels in a rabbit model of S. aureus osteomyelitis. Four of these immunogens were chosen as candidate antigens, and 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 (n=14), with a second vaccination given ten days later. Ten days following the boost, the animals were challenged through inoculation into the left tibia with MRSA. Two weeks after challenge, vaccine efficacy was analyzed through evaluation of clinical, radiological, and bacterial signs of infection compared to unvaccinated controls (n=16). None of the vaccinated rabbits showed clinical signs of infection compared to the significantly higher proportion of unvaccinated rabbits (57%) that demonstrated these signs (P < 0.0085). Also, vaccinated rabbits had significantly better radiological scores (P < 0.015) and had an 85% reduction in CFU levels in the infected bone compared to the control group. Therefore, this vaccine was able to significantly abrogate the clinical and radiological signs of osteomyelitis in a rabbit model of disease, while also greatly diminishing S. aureus colony counts in the infected bone. This is the first work to test the protective efficacy of biofilm-specific proteins when used as a vaccine in a biofilm model of infection, giving us a new way to possibly prevent these devastating, chronic diseases.