Multimechanistic Monoclonal Antibody Combination Targeting Key Staphylococcus aureus Virulence Determinants in a Rabbit Model of Prosthetic Joint Infection

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Abstract
In a rabbit model of methicillin-resistant S. aureus prosthetic joint infection, prophylaxis with AZD6389*—a combination of three monoclonal antibodies targeting alpha-hemolysin, bicomponent cytotoxins (LukSF/LukED/HlgAB/HlgCB), and clumping factor A—resulted in significant reductions in joint swelling, erythema, intra-articular pus, and bacterial burden in synovial tissues and biofilm-associated prosthetic implants when compared with isotype-matched control IgG. Targeting specific staphylococcal virulence factors could thus have potential clinical utility for prevention of prosthetic joint infection.
Funding Information
  • Monahan Foundation
  • Shanghai Jiao Tong University Affiliated Sixth People's Hospital
  • College des Enseignants de Maladies Infectieuses et Tropicales
  • Franco American Commission Fulbright
  • AstraZeneca
  • Université Claude Bernard Lyon 1

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