VACCINATION WITH A RECOMBINANT FRAGMENT OF COLLAGEN ADHESIN PROVIDES PROTECTION AGAINST STAPHYLOCOCCUS AUREUS-MEDIATED SEPTIC DEATH

Staphylococcus aureus is a major cause of nosocomial and community-acq uired infections. Morbidity and mortality due to infections such as se psis, osteomyelitis, septic arthritis, and invasive endocarditis remai n high despite the use of antibiotics. The emergence of antibiotic res istant super bugs mandates that alternative strategies for the prevent ion and treatment of S. aureus infections are developed. We investigat ed the ability of vaccination with a recombinant fragment of the S. au reus collagen adhesin to protect mice against sepsis-induced death, Ac tively immunized NMRI mice were intravenously inoculated with the S. a ureus clinical isolate strain Phillips. 14 d after inoculation, mortal ity in the collagen adhesin-vaccinated group was only 13%, compared wi th 87% in the control antigen immunized group (P < 0.001), To determin e if the protective effect was antibody mediated, we passively immuniz ed naive mice with collagen adhesin-specific antibodies. Similar to th e active Immunization strategy, passive transfer of collagen adhesin-s pecific antibodies protected mice against sepsis-induced death. In vit ro experiments indicated that S. aureus opsonized with sera from colla gen adhesin immunized mice promoted phagocytic uptake and enhanced int racellular killing compared with bacteria opsonized with sera from con trol animals,These results indicate that the collagen adhesin is a via ble target in the development of immunotherapeutics against S. aureus.