Surface polysaccharides of pathogenic bacteria, including capsular polysaccharides and lipopolysaccharides, may serve as virulence factors amd protective antigens. The age-related immunogenicity and T-cell independence of polysaccharides limit their use as vaccines. Binding to medically-useful proteins both increases their immunogenicity and confers T-cell dependence to these polysaccharides. Infants were injected with Pn6B-TT at 3, 4 and 6 months of age or at 7 and 9 months of age with only minor local reactions. Anti-Pn6 of the three Ig classes, with booster responses, were induced. There was a good correlation between IgG anti-type 6B levels and opsonophagocytic killing of the organism in-vitro. LPS of Shigella sonnei and flexneri 2a were detoxified, their O-specific polysaccharides bound to bacterial toxoids and shown to be immunogenic in mice. Phase 1 and Phase 2 studies showed these conjugates were safe and elicited long-lived antibodies at similar levels to those of adult patients following shigellosis. In a Phase 3 trial, S. sonnei-rEPA protected army recruits during outbreaks of shigellosis caused by this pathogen. These conjugates were shown to be safe and immunogenic in 4-7 year old children. Phase 3 trials have been postponed while new and more immunogenic Shigella conjugates are being evaluated in Phase 1 studies. A double mutant of Bordetella pertussis, producing a non-toxic CRM toxin and deficient in FHA synthesis, is being developed. The objective is to use this genetically-produced and more easily purified pertussis toxoid as a carrier for pneumococcus type 14 polysaccharide. Infants immunized with Pn6B-TT responded with anti-Pn6B, mostly of the IgG isotype. These antibodies had opsonophagocytic activities, correlated to their levels as measured by ELISA and RIA.
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