Design and synthesis of reagents for generation and characterization of high-affinity antibodies for a Staphylococcus...

Staphylococcus aureus is a common, opportunistic pathogen, and drug resistance of this organism continues to rise. Substantial efforts have been made to generate vaccines that provide long-lasting protection; however, these have fallen short. High-affinity antibodies could represent a useful treatment modality, taking advantage of effector functions to eliminate infecting bacteria. Many bacteria evade strong immune responses by encasing themselves in carbohydrate polymers. We have developed a means of generating high-affinity antibodies to small carbohydrate epitopes from bacteria. We describe here the design and synthesis of a disaccharide glycan from the capsular polysaccharide of S. aureus serotype 8, along with a selection/detection reagent for the characterization of antibody affinity for the targeted glycan. These materials were applied by conjugation of the disaccharide epitope to an immunogenic Qβ virus-like particle carrier protein with complete control of the position of attachment, generating a well-defined polyvalent immunogen. Without the use of additional adjuvants, this material generated a potent and long-lasting anti-glycan serum IgG response dominated by Th1 T cell help.