PILOT STUDY TO DEVELOP A VACCINE AGAINST STAPHYLOCOCCUS AUREUS INFECTION IN ARTHROPLASTY

Abstract

Most infections in arthroplasty are caused by staphylococci, about half being due to S. aureus. One of the most worrying aspects of this organism, and particularly of MRSA, is increasing multiple drug resistance, so that antimicrobial prophylaxis is probably already compromised. Vaccination offers a novel approach to overcome this. Detailed consideration of the pathogenesis of prosthesis–related infection indicates that a) prosthetic material rapidly becomes coated after implantation with plasma–derived conditioning film, and b) attachment of the bacteria to the conditioning film, by means of specific bacterial surface binding proteins, is an essential primary event. We hypothesise that antibodies to these binding proteins will block bacterial adhesion to the prosthesis, so reducing the incidence of infection. The aim of this research was to determine the effect of specific antibodies to two binding proteins (fibronectin - and fibrinogen–binding proteins, Fnbp and Fgbp respectively) on bacterial adherence to orthopaedic biomaterials coated with plasma conditioning film.

Antibodies to recombinant sequences of Fnbp and Fgbp were raised in rabbits. A strain of S. aureus bearing a genetically inserted fluorescent reporter (GFP) was used. Orthopaedic biomaterials (steel, titanium and PMMA) were coated with FFP–derived conditioning film, placed in a specially–designed flow cell and exposed to a flow of S. aureus for 3h. Images were captured every 15min and analysed for adherent bacteria using image analysis software. The experiment was repeated in the presence of the antibodies and the results compared.

Each antibody reduced the number of bacteria binding to all three materials by greater than 50%. Combining the two antibodies gave similar results to those when they were used individually.

These preliminary results suggest that while further research is required, vaccination aimed at blocking bacterial attachment to conditioning film on implanted prostheses might reduce the incidence of S. aureus infection in arthroplasty. If so, this would apply even to MRSA. Questions remaining to be addressed include the clinical relevance of a 50% reduction in attachment, and future research will attempt to link this to a reduction in infection.