HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

细菌病原体的表面多糖起保护作用

The surface polysaccharides of bacterial pathogens serve as protective antigens. Their immunologic properties, namely their age-related and T- independent immunogenicity, limit their use as vaccines. Covalent attachment to medically-useful proteins to form conjugates, both increases their immunogenicity and confers T-dependent properties to these polysaccharides. The capsular polysaccharides of Streptococcus pneumococcus types 6B and 14, Staphylococcus aureus types 5 and 8, Group B streptococcus type 3, Haemophilus influenzae type a and Escherichia coli K1 were bound to proteins and their immunologic properties assayed in mice. Pneumococcal type 6B and Group B streptococcal conjugates have been evaluated clinically. The safety of conjugate-induced antibodies reactive with E. coli K1 was evaluated in an infant rat model. LPSs of shigellae were detoxified, their O-specific polysaccharides bound to bacterial toxoids and their immunogenicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these O-specific polysaccharides were safe and immunogenic: LPS antibody levels elicited by the investigational conjugates were similar to those in recruits convalescent from shigellosis. In preliminary studies, a S. sonnei-rEPA conjugate protected against shigellosis caused by this pathogen. Extensive efficacy trials are underway.