The Human Antibody Response to Staphylococcus Aureus in Colonization and Infection

__Abstract_

Introduction: Treatment options for Staphylococcus aureus infections are becoming increasingly limited because of the extensive emergence of antimicrobial resistance among S. aureus isolates. Consequently, novel approaches, including vaccines and immunotherapy, are urgently needed. In order to develop such alternative strategies, a better understanding of the human antibody response to S. aureus exposure, is necessary. Methods: The qualitative and quantitative levels of antibodies directed to important S. aureus cell wall-associated proteins, immune-modulating proteins and toxins were measured in healthy individuals, children and patients suffering from diverse S. aureus infections. A flow cytometry technique based on differentially coloured microspheres was used (xMAP® Technology). Results: In patients as well as in healthy children and adults, the antistaphylococcal antibody profiles showed extensive inter-individual variability. When groups were compared and significant differences were found, the level of antistaphylococcal antibodies was higher in the group that was more frequently exposed to S. aureus (e.g. persistent carriers vs. non-carriers, colonized vs. non-colonized children, infected patients vs. controls, adults vs. children). However, the significant levels of S. aureus antigen-specific IgG and IgA in persistent carriers were not sufficient to eliminate S. aureus from the nose. Furthermore, maternally derived IgG antibodies specifically directed at staphylococcal antigens did not protect the young infant against S. aureus nasal colonization. In addition, despite of the significant levels of antistaphylococcal antibodies in persistent carriers and S. aureus infected patients, the bacterium still manages to cause infection. Conclusion:Our data do not support the concept that anti-S. aureus antibodies will be protective. Therefore, attempts to prevent or treat colonization or infection through passive immunization approaches are not likely to succeed.