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Antimicrobial Agents and Chemotherapy, February 2006, p. 511-518, Vol. 50, No. 2
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.2.511-518.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Immunoglobulin G Recognizing Fibrinogen-Binding Surface Proteins Is Protective against both Staphylococcus aureus and Staphylococcus epidermidis Infections In Vivo

John H. Vernachio,1* Arnold S. Bayer,2,3 Brenda Ames,1 Dawn Bryant,1 Bradley D. Prater,1 Peter J. Syribeys,1 Elena L. Gorovits,1 and Joseph M. Patti1

Inhibitex, Inc., Alpharetta, Georgia,1 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California,2 The Geffen School of Medicine at UCLA, Los Angeles, California3

Received 24 May 2005/ Returned for modification 19 September 2005/ Accepted 30 November 2005

A human donor-selected immunoglobulin G for intravenous injection (IGIV) product with elevated titers against the staphylococcal fibrinogen-binding MSCRAMM proteins ClfA and SdrG (INH-A21) was tested in vitro and in vivo. INH-A21 contained a significantly increased ability to inhibit the fibrinogen-binding activity of recombinant forms of both ClfA and SdrG. Evaluation of the opsonizing potential of INH-A21 was evaluated using fluorescently labeled bacteria; this assay indicated an increase in phagocytic activity compared to normal IGIV. The prophylactic efficacy of INH-A21 against an intraperitoneal challenge of methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a neonatal rat model. INH-A21 was also evaluated for prophylactic and therapeutic efficacy in a rabbit model of catheter-induced aortic valve infective endocarditis caused by either MRSE or methicillin-resistant Staphylococcus aureus (MRSA). Results from the in vivo models demonstrated potent prophylactic and therapeutic efficacy against both MRSE and MRSA. These data suggest that INH-A21 may be an important tool for the prevention and treatment of staphylococcal infections, especially in high-risk populations.

* Corresponding author. Mailing address: Inhibitex, Inc., 9005 Westside Parkway, Alpharetta, GA 30004. Phone: (678) 746-1160. Fax: (678) 746-0628. E-mail: jvernachio{at}inhibitex.com.

Antimicrobial Agents and Chemotherapy, February 2006, p. 511-518, Vol. 50, No. 2
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.2.511-518.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sellman, B. R., Timofeyeva, Y., Nanra, J., Scott, A., Fulginiti, J. P., Matsuka, Y. V., Baker, S. M. (2008). Expression of Staphylococcus epidermidis SdrG Increases following Exposure to an In Vivo Environment. Infect. Immun. 76: 2950-2957 [Abstract] [Full Text]  


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