Bacterial Polysaccharide Vaccines: Analytical Perspectives

Abstract

Many bacterial pathogens express cell surface polysaccharides which protect the bacterium during the initial stages of infection and hide the cell surface from innate host immune defense mechanisms. In some cases, pre-existing antibodies directed against these cell surface polysaccharides protect against infection: in these cases the purified polysaccharides can be used as prophylactic vaccines. Purified polysaccharide vaccines prepared from capsular polysaccharides (CPSs) present several unique features. The polysaccharides are relatively simple, and, in the absence of accessible animal models, quality control is largely based on physicochemical and immunochemical methods, and dosage is in SI units. As protection is serotype- (or serogroup-) specific, polysaccharide vaccines are often blends of multiple polysaccharides derived from different strains, e.g., 23 in the case of pneumococcal vaccines. Critical quality attributes for these vaccines are polysaccharide identity, polysaccharide molecular size, and safety factors (such as pyrogenicity). As T cell-independent Type II immunogens, these vaccines fail to invoke immunological memory, so that repeat immunization is required. They are poorly immunogenic in infants, the principal risk group for many of these infections, and technologies such as saccharide conjugation to carrier proteins have been developed to protect this group, while polysaccharide vaccines continue to be used in adolescents and adults. In this chapter, we present background on the physical chemical nature of bacterial polysaccharides, their Critical Quality Attributes (CQA’s), and the analytical methodologies applied to their structural and physical characterization as well as to measure their CQA’s.