This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hall, A. E. Articles by Patti, J. M. Search for Related Content PubMed PubMed Citation Articles by Hall, A. E. Articles by Patti, J. M.

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

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.

Editor: F. C. Fang

This article has been cited by other articles:

• Bekeredjian-Ding, I., Inamura, S., Giese, T., Moll, H., Endres, S., Sing, A., Zahringer, U., Hartmann, G. (2007). Staphylococcus aureus Protein A Triggers T Cell-Independent B Cell Proliferation by Sensitizing B Cells for TLR2 Ligands. J. Immunol. 178: 2803-2812 [Abstract] [Full Text]  
• Procopio Evagrio George, N., Wei, Q., Kyun Shin, P., Konstantopoulos, K., Ross, J. M. (2006). Staphylococcus aureus Adhesion via Spa, ClfA, and SdrCDE to Immobilized Platelets Demonstrates Shear-Dependent Behavior. Arterioscler. Thromb. Vasc. Bio. 26: 2394-2400 [Abstract] [Full Text]  
• Weems, J. J. Jr., Steinberg, J. P., Filler, S., Baddley, J. W., Corey, G. R., Sampathkumar, P., Winston, L., John, J. F., Kubin, C. J., Talwani, R., Moore, T., Patti, J. M., Hetherington, S., Texter, M., Wenzel, E., Kelley, V. A., Fowler, V. G. Jr. (2006). Phase II, Randomized, Double-Blind, Multicenter Study Comparing the Safety and Pharmacokinetics of Tefibazumab to Placebo for Treatment of Staphylococcus aureus Bacteremia.. Antimicrob. Agents Chemother. 50: 2751-2755 [Abstract] [Full Text]  
• Pourmand, M. R., Clarke, S. R., Schuman, R. F., Mond, J. J., Foster, S. J. (2006). Identification of Antigenic Components of Staphylococcus epidermidis Expressed during Human Infection.. Infect. Immun. 74: 4644-4654 [Abstract] [Full Text]  
• Kuklin, N. A., Clark, D. J., Secore, S., Cook, J., Cope, L. D., McNeely, T., Noble, L., Brown, M. J., Zorman, J. K., Wang, X. M., Pancari, G., Fan, H., Isett, K., Burgess, B., Bryan, J., Brownlow, M., George, H., Meinz, M., Liddell, M. E., Kelly, R., Schultz, L., Montgomery, D., Onishi, J., Losada, M., Martin, M., Ebert, T., Tan, C. Y., Schofield, T. L., Nagy, E., Meineke, A., Joyce, J. G., Kurtz, M. B., Caulfield, M. J., Jansen, K. U., McClements, W., Anderson, A. S. (2006). A Novel Staphylococcus aureus Vaccine: Iron Surface Determinant B Induces Rapid Antibody Responses in Rhesus Macaques and Specific Increased Survival in a Murine S. aureus Sepsis Model. Infect. Immun. 74: 2215-2223 [Abstract] [Full Text]  
• Maira-Litran, T., Kropec, A., Goldmann, D. A., Pier, G. B. (2005). Comparative Opsonic and Protective Activities of Staphylococcus aureus Conjugate Vaccines Containing Native or Deacetylated Staphylococcal Poly-N-Acetyl-{beta}-(1-6)-Glucosamine. Infect. Immun. 73: 6752-6762 [Abstract] [Full Text]  
• Domanski, P. J., Patel, P. R., Bayer, A. S., Zhang, L., Hall, A. E., Syribeys, P. J., Gorovits, E. L., Bryant, D., Vernachio, J. H., Hutchins, J. T., Patti, J. M. (2005). Characterization of a Humanized Monoclonal Antibody Recognizing Clumping Factor A Expressed by Staphylococcus aureus. Infect. Immun. 73: 5229-5232 [Abstract] [Full Text]  
• Goerke, C., Fluckiger, U., Steinhuber, A., Bisanzio, V., Ulrich, M., Bischoff, M., Patti, J. M., Wolz, C. (2005). Role of Staphylococcus aureus Global Regulators sae and {sigma}B in Virulence Gene Expression during Device-Related Infection. Infect. Immun. 73: 3415-3421 [Abstract] [Full Text]  
• Dryla, A., Prustomersky, S., Gelbmann, D., Hanner, M., Bettinger, E., Kocsis, B., Kustos, T., Henics, T., Meinke, A., Nagy, E. (2005). Comparison of Antibody Repertoires against Staphylococcus aureus in Healthy Individuals and in Acutely Infected Patients. CVI 12: 387-398 [Abstract] [Full Text]  
• Liu, Y., Ames, B., Gorovits, E., Prater, B. D., Syribeys, P., Vernachio, J. H., Patti, J. M. (2004). SdrX, a Serine-Aspartate Repeat Protein Expressed by Staphylococcus capitis with Collagen VI Binding Activity. Infect. Immun. 72: 6237-6244 [Abstract] [Full Text]  
• Sillanpaa, J., Xu, Y., Nallapareddy, S. R., Murray, B. E., Hook, M. (2004). A family of putative MSCRAMMs from Enterococcus faecalis. Microbiology 150: 2069-2078 [Abstract] [Full Text]