HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

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The surface polysaccharides of bacterial pathogens, which include capsular polysaccharides and lipopolysaccharides, serve as protective antigens. The immunologic properties of these bacterial polysaccharides, namely their age-related and T-cell independent immunogenicity, limit their use as vaccines. Covalently attachment to medically-useful proteins to form conjugates, both increases their immunogenicity and confers T-cell dependent properties to these polysaccharides. The capsular polysaccharides of Streptococcus pneumococcus type 6B, Staphylococcus aureus types 5 and 8, Group B streptococcus type 3 have been bound to several proteins and evaluated clinically. S. aureus type 5-rEPA was evaluated in end stage renal disease patients; type 5 antibodies of the three major Ig classes rose significantly though to a lesser degree than in healthy volunteers, no booster response to reinjection at 6 weeks was found. These antibodies had opsonophagocytic activities. Pn6B-TT was evaluated in patients with sickle cell disease, healthy infants at 3, 4 and 6 months of age or at 7 and 9 months of age. Type specific antibodies of the three Ig classes, with booster responses, were induced. The magnitude of these responses was lesser than of Hib- TT. GBSIII-TT was evaluated in females of child bearing age. IgG antitype III rose similarly to the response to the polysaccharide alone. Technical problems with this lot were identified. All conjugates were safe, with only minor local reaction. The LPS of shigellae was detoxified, their O-specific polysaccharides bound to bacterial toxoids and their immunogennicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these conjugates of the 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. A more extensive study showed protection of 75%.