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Infection and Immunity, December 2003, p. 6864-6870, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6864-6870.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization of a Protective Monoclonal Antibody Recognizing Staphylococcus aureus MSCRAMM Protein Clumping Factor A

Andrea E. Hall,1 Paul J. Domanski,1 Pratiksha R. Patel,1 John H. Vernachio,1 Peter J. Syribeys,1 Elena L. Gorovits,1 Michael A. Johnson,2 Julia M. Ross,2 Jeff T. Hutchins,1 and Joseph M. Patti1*

Inhibitex, Inc., Alpharetta, Georgia,1 Department of Chemical and Biochemical Engineering, University of Maryland, Baltimore, Maryland2

Received 6 June 2003/ Returned for modification 21 July 2003/ Accepted 2 September 2003

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.

* Corresponding author. Mailing address: Inhibitex, Inc., 1165 Sanctuary Parkway, Suite 400, Alpharetta, GA 30004. Phone: (678) 746-1144. Fax: (678) 336-1214. E-mail: jpatti{at}inhibitex.com.

Editor: F. C. Fang

Infection and Immunity, December 2003, p. 6864-6870, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6864-6870.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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