The increasing use of carbohydrate-based conjugate vaccines is founded on the observation that antibodies against the type-specific bacterial capsular polysaccharides (CPSs) are often protective and is driven by the increasing prevalence of antibiotic resistant strains. However, the relationships between the carbohydrate sequence and antigenicity (affinity and specificity for antibody) or immunogenicity (ability to induce an antibody response) are poorly understood.<br/> <br/>Here we will illustrate that computational methods can provide unique insight into the structural features of antigenic oligosaccharides that are responsible for mediating the affinity and specificity of their interactions with type-specific monoclonal antibodies (mAbs). This is an area of research that presents severe challenges for traditional 3D structural methods; however, simulational methods are well suited to addressing some of these challenges. In particular, they offer the opportunity to generate experimentally inaccessible data, to provide an atomic level interpretation for macroscopic or indirect experimental data, to interpolate between sparse experimental data points, to identify putative antigen – antibody interactions that may be experimentally probed, and to quantify the roles of enthalpy and entropy in driving oligosaccharide antigenicity. Such insight could form a basis for the rational development of more effective antibacterial vaccines and conversely higher affinity engineered carbohydrate- binding antibodies.<br/>

Defining carbohydrate antigenicity: How are flexible molecules recognized by the immune system?

254th National Meeting (2017)

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