The surface polysaccharides of bacterial pathogens including 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 have been bound to tetanus toxoid 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 compared to healthy volunteers. As expected, there was no booster response to reinjection. These vaccine-induced 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. All conjugates were safe, with only minor local reaction. The LPS of shigellae was detoxified, their 0-specific polysaccharides bound to bacterial toxoids and their immunogenicity in mice found to be satisfactory. In Phase 1 and Phase 2 studies, these conjugates of the 0-specific polysaccharides were safe and immunogenic: LPS antibody levels elicited by the investigational conjugates were similar to those in recruits convalescent from shigellosis vaccine- induced IgG persisted at high levels for two years. In preliminary though statistically significant studies, a S. sonnei-rEPA conjugate protected against shigellosis caused by this pathogen. A phase 2 study of S. sonnei and S. flexneri in children showed both conjugates to be highly safe and immunogenic. Phase 3 trials are being planned.
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