| A number of polysaccharide-based vaccines have been developed to stimulate protective immunity against certain encapsulated bacteria. Because of the T cell-independent nature of polysaccharide antigens, the antibody response stimulated by such vaccines is of limited magnitude and restricted isotype, lacks avidity maturation, and is not boosted following reimmunization. Using as a model of the antibody response of mice to the type 3 capsular polysaccharide (S-III) of Streptococcus pneumoniae, the purpose of this project was to develop a vaccine, which by virtue of its formulation and application, would stimulate a heightened antibody response. Three approaches have been taken to develop such a vaccine.;The first approach was to alter the nature of the response stimulated by the antigen to one which is T cell dependent. By conjugating S-III to a protein carrier, the toxoided vaccine of staphylococcal enterotoxin B (SEB), a conjugate vaccine (S-III-SEB) has been synthesized. In contrast to the response stimulated by intraperitoneal immunization with purified S-III, the S-III-specific antibody response stimulated by this S-III-SEB conjugate vaccine was of greater magnitude and altered isotype profile and was boosted by reimmunization.;The second approach was to deliver this conjugate vaccine in a manner to further enhance the antibody response. A novel microcapsule delivery system, where the conjugate vaccine was coated with biocompatible and biodegradable copolymers of DL-lactide and glycolide (DL-lactide-co-glycolide), has been employed. These microcapsules, which are rapidly taken up by phagocytic cells following intraperitoneal or intratracheal injection, effectively delivered antigen to the site of immune response initiation. The plasma anti-S-III response following secondary intraperitoneal immunization with microencapsulated S-III-SEB approached 200 times the level of the response stimulated by an optimal dose of purified S-III.;The third approach was to deliver the vaccine by an immunization route which stimulates antibodies at the site of infection. Intratracheal immunization with microencapsulated S-III-SEB stimulated heightened IgA and IgG anti-S-III concentrations in the circulation and in the secretions which bathe the mucosal surfaces of the lungs and the oral cavity. |
