Human immunoglobulin G recognizing fibrinogen-binding surface proteins is protective against both Staphylococcus aureus and Staphylococcus epidermidis infections in vivo.
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.
Vernachio
John H
JH
Inhibitex, Inc., 9005 Westside Parkway, Alpharetta, GA 30004, USA. jvernachio@inhibitex.com
Bayer
Arnold S
AS
Ames
Brenda
B
Bryant
Dawn
D
Prater
Bradley D
BD
Syribeys
Peter J
PJ
Gorovits
Elena L
EL
Patti
Joseph M
JM
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*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003030:Coagulase; C112556:Fbe protein, bacteria; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous