Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice

Skurnik, D., et al. J Clin invest. 2010; 120 (9): 3220-3233

Speaker: Chun-Hsien Fei (費俊憲)                               Time: 14:10~15:00, Nov. 24, 2010

Commentator: Dr. Chun-Keung Yu (余俊強老師)       Place: Room 601

Abstract

        The prevalence of methicillin-resistant S. aureus has become a serious problem in nosocomial and community-acquired infections because of ineffective usage of antibiotics and increasing antibiotic resistance. Given the high recurrence rate and mortality¹, an S. aureus vaccine is needed to control the disastrous situation. In this paper, the authors aimed to understand the protective immunity against S. aureus that might contribute to future vaccine development. Human immunity to extracellular pathogens is mediated by opsonic killing (OPK) through antibodies to surface polysaccharides, capsular polysaccharide (CP) and poly-N-acetyl glucosamine (PNAG). Either CP or PNAG induced polyclonal animal antisera and monoclonal antibodies have shown potent OPK activity (OPKA), but, surprisingly, the activity was reduced when they were mixed together. Two mouse models of S. aureus infection, bacteremia and skin infection, were used and passive protection was reduced. Loss of complement deposition and antibodies binding to the bacterial surface were seen in combined antisera. Aggregation of two monoclonal antibodies to CP and PNAG was visualized under Electron microscopy. Antibody interaction was further confirmed by isothermal calorimetry and surface Plasmon resonance, and the results showed that antibodies to CP and PNAG bound to each other via an idiotype-anti-idiotype interaction. This phenomenon was also found in human sera with S. aureus bacteremia. These findings might explain the failure antibody immunity to S. aureus infections due to interference in OPKA when both antibodies to CP and PNAG are present. This information could provide new approaches to vaccine design.

Reference

1.      Sara E. Cosgrove, et al. Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-Analysis. clinical infection disease. 2003; 36 (1): 53-59.