Coagulases as determinants of protective immune responses against Staphylococcus aureus

Infect Immun. 2012 Oct;80(10):3389-98. doi: 10.1128/IAI.00562-12. Epub 2012 Jul 23.

Abstract

During infection, Staphylococcus aureus secretes two coagulases (Coa and von Willebrand factor binding protein [vWbp]), which, following an association with host prothrombin and fibrinogen, form fibrin clots and enable the establishment of staphylococcal disease. Within the genomes of different S. aureus isolates, coagulase gene sequences are variable, and this has been exploited for a classification of types. We show here that antibodies directed against the variable prothrombin binding portion of coagulases confer type-specific immunity through the neutralization of S. aureus clotting activity and protection from staphylococcal disease in mice. By combining variable portions of coagulases from North American isolates into hybrid Coa and vWbp proteins, a subunit vaccine that provided protection against challenge with different coagulase-type S. aureus strains in mice was derived.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology*
  • Binding Sites
  • Coagulase / genetics
  • Coagulase / immunology*
  • Coagulase / metabolism
  • Female
  • Gene Expression Regulation, Bacterial / immunology*
  • Gene Expression Regulation, Enzymologic / immunology*
  • Genome, Bacterial
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Protein Binding
  • Rabbits
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control
  • Staphylococcal Vaccines / immunology
  • Staphylococcus aureus / classification
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / immunology*
  • Time Factors

Substances

  • Antibodies, Bacterial
  • Coagulase
  • Staphylococcal Vaccines