title: Human immunoglobulin G recognizing fibrinogen-binding surface proteins is protective against both Staphylococcus aureus and Staphylococcus epidermidis infections in vivo.
abstract: 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.
authors.affiliation: Inhibitex, Inc., 9005 Westside Parkway, Alpharetta, GA 30004, USA. jvernachio@inhibitex.com
authors.forename: John H
authors.initials: JH
authors.lastname: Vernachio
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
authors.forename: Brenda
authors.initials: B
authors.lastname: Ames
authors.forename: Dawn
authors.initials: D
authors.lastname: Bryant
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Prater
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Syribeys
authors.forename: Elena L
authors.initials: EL
authors.lastname: Gorovits
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Patti
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D003030:Coagulase / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003030:Coagulase; C112556:Fbe protein, bacteria; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous