The neutralizing effects of hyperimmune antibodies against extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus

Abstract

Staphylococcus aureus is a significant cause of acute and chronic infection and boasts a diverse array of virulence factors. S. aureus produces and secretes a protein, extracellular fibrinogen (Fg)-binding protein (Efb), which contributes to virulence in wound infection. Efb binds to both Fg and platelets and inhibits platelet function in vitro and in vivo. In this study, we have characterized the antibody response against Efb. Antibodies generated in response to immunization with Efb can neutralize the biological effects of Efb. Hyperimmune sheep immunoglobulin (Ig)G against Efb blocked the binding of Efb to Fg and prevented Efb-mediated inhibition of platelet aggregation. Furthermore, these antibodies cross-reacted with coagulase and blocked coagulase activity in plasma. Immunization of mice with Efb resulted in the generation of high titre specific antibodies. When subjected to a foreign-body-associated wound infection, the vaccinated animals developed significantly less severe wound infection than the unvaccinated controls. Also, human IgG against Efb was prepared from commercial IgG pools; however, the monospecific human anti-Efb that was enriched was unable to neutralize Efb. We conclude that immunization with Efb is required in order to generate a protective antibody response to Efb from S. aureus. © 2006 Blackwell Publishing Ltd.