IN-VITRO ASSESSMENT OF STAPHYLOCOCCUS AUREUS FIBRONECTIN-BINDING PROTEIN-A (FNBP-A) AS A POTENTIAL VACCINE ANTIGEN FOR PREVENTION OF INFECTION OF ORTHOPAEDIC IMPLANTS.

Abstract

Background: Prosthetic joint infection (PJI) is most commonly caused by skin-derived, biofilm-forming staphylococci, with Staphylococcus aureus being most virulent and MRSA becoming a substantial problem. Cephaloporins are almost universally used as prophylaxis against PJI, yet Methicillin - resistant S aureus (MRSA) is becoming increasingly common in hospitals, nursing homes and now in the community. Such strains are not susceptible to cephalorsporins or to a range of other antimicrobials. In view of this increasing antibiotic resistance, an alternative approach to preventing S. aureus PJI is needed, and we propose that vaccination is a promising approach. Having regard to the distinct pathogenesis of PJI, this must target key events in infection establishment, such as adhesion to the implant, via the plasma conditioning film, mediated by bacterial binding proteins. It must also have the potential to protect against all S. aureus regardless of antibiotic resistance profile. Fibronectin-binding protein-A (FnBP-A) is one example, but the potential of FnBP-A as a PJI vaccine candidate has not been thoroughly investigated and data in previous literature are contradictory.

Methods: Here, polyclonal rabbit antibody against recombinant(r) FnBP-A binding domain was produced and investigated for the first time for activity against S. aureus adhesion to rabbit plasma-conditioned steel coupons in-vitro.

Results: The adhesion of homologous S. aureus 8325-4 (fnbA+, fnbB+), and a heterologous MRSA arthroplasty isolate was significantly (p < 0.05) reduced when pre-exposed to anti-FnBP-A antiserum (un-purified and IgG-purified), compared to pre-exposure with pre-immune serum. This was not observed with mutant strain S. aureus DU5883 (fnbA?, fnbB?), indicating the involvement of FnBP-A – specific inhibitory antibody (IgG). Results clearly demonstrate the potential of rFnBP-A binding domain as a vaccine antigen for prevention of PJI and merit further investigation.

The implications of this are that vaccination using this peptide might be expected to protect patients about to undergo elective arthroplasty from infection with S aureus whatever its antibiotic susceptibility, so offering a realistic solution to the problem of increasing resistance.