Cloning and characterization of a gene for any 19 kDa fibrinogen-binding protein from Mol. repertoires of healthy individuals with or without carriage, as well as in those NRC-AN-019 of patients in the acute phase of contamination. Most importantly, we recognized antigenic proteins for which specific antibodies were missing or underrepresented in infected patients. In contrast to the well-described transient nature of disease-induced antistaphylococcal immune response, it was demonstrated that high-titer antistaphylococcal antibodies are stable for years in healthy individuals. In addition, we provide evidence obtained on the basis of opsonophagocytic and neutralizing activity in vitro assays that circulating antistaphylococcal serum antibodies in healthy donors are functional. In light of these data we suggest that proper serological analysis comparing the preexisting antibody repertoires of hospitalized patients with different outcomes for nosocomial staphylococcal infections could be extremely useful for the evaluation of candidate vaccine antigens in addition to protection data generated with animal models. is one of the most common bacterial causes of infections in both hospitals and communities and imposes a medical problem of increasing severity (5, 12). Coagulase-positive is the most pathogenic staphylococcal species and an opportunistic pathogen that can cause illnesses ranging from minor infections to life-threatening diseases. The high incidence of staphylococcal infections is related to an increase in the use of catheters and prosthetic devices and in the number of immunity-compromised patients. Importantly, the emergence and the disease-causing capacity of staphylococci are strongly related to the common use of antibiotics combined with the enormous potential of this bacterium to develop multidrug resistance (31, 45). Moreover, the most severe staphylococcal infections are still associated with high mortality, despite the availability of effective antibiotics. As a consequence, new medical treatment regimens are needed in the management of staphylococcal diseases. Immunological methods such as antistaphylococcal vaccination certainly have the potential for preventive and therapeutic treatment. However, FST despite the high prevalence of and medical need to prevent infections in the human population, our understanding of the immune correlates of protection in general and our knowledge of the staphylococcal antigens that are recognized by the human immune system particularly are still incomplete. Staphylococci are primarily extracellular pathogens; consequently, host defense relies mainly on innate immunological mechanisms supported by antistaphylococcal adaptive humoral responses. This notion is usually well supported by the increased frequency of staphylococcal infections among individuals deficient in antibodies (hypo- and agammaglobulinemias) and neutrophil function (30). In spite of the ability of the organism to produce a large number of NRC-AN-019 toxins and extracellular products, the hallmarks of infections are dissemination through the blood and multiplication that can be most efficiently controlled by phagocytosis. NRC-AN-019 Thus, complement-mediated opsonization is essential for the removal of by the human host (9). Although it has been shown that serum immunoglobulin (Ig) preparations can neutralize toxins from in in vitro assays (10, 18), further studies are needed to determine the importance and involvement of circulating human antibodies in protection. Previously, several studies have investigated the human immune response to in infected patients but only a few have investigated the response in apparently healthy individuals. In most of the serological studies, antibody levels against total bacterial lysates or few selected proteins were decided and increased levels were measured in convalescing patients (4, 7, 8, 48). Further evidence for the role of antibodies in protection comes from experimental studies NRC-AN-019 conducted with animals. It has been shown that antibodies against NRC-AN-019 certain bacterial components of antigens of healthy individuals and acute-phase patients with documented staphylococcal contamination. The comparison of antibody levels and responses might thus identify missing antibodies that contribute to disease susceptibility or early antigens that induce antibody responses at disease onset. In addition, we evaluated the relationship between levels and functionality of antibodies in vitro. MATERIALS AND METHODS Human serum samples. Sera were collected from healthy individuals without evidence of contamination and from patients in the acute phase of diseases caused by infections such as wound contamination (17 subjects),.
ALK Receptors