Vaccination with a recombinant fragment of collagen adhesin provides protection against Staphylococcus aureus-mediated septic death

Ing Marie Nilsson, Joseph M. Patti, Tomas Bremell, Magnus Höök, Andrzej Tarkowski

    Research output: Contribution to journalArticlepeer-review

    150 Scopus citations

    Abstract

    Staphylococcus aureus is a major cause of nosocomial and community- acquired infections. Morbidity and mortality due to infections such as sepsis, osteomyelitis, septic arthritis, and invasive endocarditis remain high despite the use of antibiotics. The emergence of antibiotic resistant super bugs mandates that alternative strategies for the prevention and treatment of S. aureus infections are developed. We investigated the ability of vaccination with a recombinant fragment of the S. aureus collagen adhesin to protect mice against sepsis-induced death. Actively immunized NMRI mice were intravenously inoculated with the S. aureus clinical isolate strain Phillips. 14 d after inoculation, mortality in the collagen adhesin- vaccinated group was only 13%, compared with 87% in the control antigen immunized group (P < 0.001). To determine if the protective effect was antibody mediated, we passively immunized naive mice with collagen adhesin- specific antibodies. Similar to the active immunization strategy, passive transfer of collagen adhesin-specific antibodies protected mice against sepsis-induced death. In vitro experiments indicated that S. aureus opsonized with sera from collagen adhesin immunized mice promoted phagocytic uptake and enhanced intracellular killing compared with bacteria opsonized with sera from control animals. These results indicate that the collagen adhesin is a viable target in the development of immunotherapeutics against S. aureus.

    Original languageEnglish (US)
    Pages (from-to)2640-2649
    Number of pages10
    JournalJournal of Clinical Investigation
    Volume101
    Issue number12
    DOIs
    StatePublished - Jun 15 1998

    Keywords

    • Antibody response
    • Intracellular killing
    • Phagocytosis
    • Sepsis
    • Staphylococcus aureus

    ASJC Scopus subject areas

    • General Medicine

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