Infection and Immunity · 2003 · 145 citations · 42 references
Life SciencesImmunologyMicrobiologyHost-pathogen InteractionsMonoclonal AntibodiesSepsisAntibody CharacterizationAntibody-antigen RecognitionBacterial Virulence FactorsMicrobial Virulence FactorsPathogen AdhesionTherapeutic Monoclonal AntibodiesAntibody-mediated Bacterial ProtectionBacterial Adhesion MechanismsBacterial Adhesion RecognitionCell Surface ProteinsMicrobial Surface RecognitionMonoclonal Antibody CharacterizationMurine ModelsVirulence Factor Expression
The Staphylococcus aureus MSCRAMM (microbial surface components recognizing adhesive matrix molecules) protein clumping factor A (ClfA) has been shown to be a critical virulence factor in several experimental models of infection. This report describes the generation, characterization, and in vivo evaluation of a murine monoclonal antibody (MAb) against ClfA. Flow cytometric analysis revealed that MAb 12-9 recognized ClfA protein expressed by all of the clinical S. aureus strains obtained from a variety of sources. In assays measuring whole-cell S. aureus binding to human fibrinogen, MAb 12-9 inhibited S. aureus binding by over 90% and displaced up to 35% of the previously adherent S. aureus bacteria. Furthermore, a single infusion of MAb 12-9 was protective against an intravenous challenge with a methicillin-resistant strain of S. aureus in a murine sepsis model (P < 0.0001). These data suggest that anti-ClfA MAb 12-9 should be further investigated as a novel immunotherapy for the treatment and prevention of life-threatening S. aureus infections.
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