Characterization of a protective monoclonal antibody recognizing Staphylococcus aureus MSCRAMM protein clumping factor A.
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.
Hall
Andrea E
AE
Inhibitex, Inc., Alpharetta, Georgia 30004, USA.
Domanski
Paul J
PJ
Patel
Pratiksha R
PR
Vernachio
John H
JH
Syribeys
Peter J
PJ
Gorovits
Elena L
EL
Johnson
Michael A
MA
Ross
Julia M
JM
Hutchins
Jeff T
JT
Patti
Joseph M
JM
D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D001422:Bacterial Adhesion; D003030:Coagulase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D020349:Surface Plasmon Resonance
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D003030:Coagulase; C048165:adhesin, Staphylococcus aureus