Group B streptococcal infection is a leading cause of neonatal sepsis. Attack rates of 2-3/1000 live births have been observed. Despite advances in diagnosis, supportive care and treatment, mortality of 10-20% is reported. Of the serological types, type III is the most frequent isolate. Studies indicate the type-specific antibody to the capsular polysaccharide is protective. The use of hyperimmune globulin containing type-specific antibodies, therefore, would be expected to be therapeutic. Native type III polysaccharide, although useful, is not optimally immunogenic. However, by covalently conjugating a polysaccharide to a protein carrier, the response to a polysaccharide can be improved by activation of T-dependent mechanisms. The method of conjugation can critically effect the activation of T-cells and recognition of the polysaccharide. Therefore, this proposal examines three different methods of preparing GBS type III polysaccharide-protein conjugates. Each conjugate will be characterized chemically and its ability to elicit antibody and activate T-dependent mechanism evaluated. Most importantly, the antibodies elicited by each vaccine candidate will be assessed for biological function in both opsonophagocytosis assays and in animal models of GBS sepsis. Ultimately, the objective is the development of a multivalent conjugate vaccine for both active immunization and the preparation of hyperimmune globulin for neonatal sepsis.
