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.

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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