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The neutralizing effects of hyperimmune antibodies against extracellular fibrinogen-binding protein, Efb, from
O Shannon1, A Uekotter, J-I Flock
1Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
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.
Insights
Immunizing with Staphylococcus aureus extracellular fibrinogen-binding protein (Efb) generates protective antibodies. These antibodies neutralize Efb
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Staphylococcus aureus is a major cause of bacterial infections.
- Extracellular fibrinogen-binding protein (Efb) is a key virulence factor in S. aureus wound infections.
- Efb binds fibrinogen and platelets, inhibiting platelet function.
Purpose of the Study:
- To characterize the antibody response against Efb.
- To determine if antibodies against Efb can neutralize its biological activity.
- To assess the protective efficacy of Efb immunization against S. aureus wound infection.
Main Methods:
- Generation of hyperimmune sheep IgG against Efb.
- In vitro assays to assess Efb-Fg binding and Efb-mediated platelet inhibition.
- In vivo mouse model of foreign-body-associated wound infection.
- Preparation and testing of human IgG against Efb.
Main Results:
- Sheep anti-Efb IgG neutralized Efb's biological effects, blocking Efb-Fg binding and platelet aggregation inhibition.
- These antibodies cross-reacted with coagulase and inhibited its plasma activity.
- Immunization of mice with Efb induced high-titer specific antibodies and reduced wound infection severity.
- Enriched human anti-Efb IgG from commercial pools did not neutralize Efb.
Conclusions:
- Antibodies generated through immunization with Efb are required for protection against S. aureus.
- Efb-specific antibodies can neutralize Efb's virulence mechanisms.
- Efb represents a potential target for vaccine development against S. aureus infections.
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