Conjugate-induced Polysaccharide Antibodies

Child Health And Human Development

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Abstract

Surface polysaccharides of Gram-negative enteric pathogens, in the form of capsule or lipopolysaccharide, are both essential virulence factors and protective antigens. The immunogenicity of these polysaccharides were enhanced by binding to carrier proteins. Sequential clinical studies in adults and in children in Vietnam, an area with a high attack rate of typhoid, showed that the capsular polysaccharide (Vi) conjugates bound to the recombinant Pseudomonas aeruginosa exoprotein A (rEPA) elicited high responses against typhi. In a Phase III trial, About 12,000 2-5 years old children injected with the conjugate vaccine showed no significant side reaction. The efficacy of Vi-rEPA was 91% after 27 months active and 88% after 28-40 months passive surveillance. Salmonella paratyphi A, the second most common cause of enteric fever in Southeast Asia, was found to be safe and immunogenic in adults, teenagers and then 2-4 year old children. Escherichia coli O157, an emerging pathogen, causes hemolytic uremic syndrome in young children. Phase 1 study of O157 O-specific polysaccharide-rEPA conjugate demonstrated safety and immunogenicity in adult volunteers. A phase 2 study in ren 2-5 year old children is planned. Non-toxic shiga toxin I is purified from mutant E. coli O157 and will be conjugated with O-specific polysaccharide for a bivalent vaccine. The major reservoir of E.coli O157 is cattle. LPS-protein conjugate showed to be immunogenic in mouse and cattle and a challenge study is planned to demonstrate the clearance of the carriage state in cattle. Vibrio cholera O1 and O139 are the major sero types in cholera infections. Conjugates synthesized with capsular polysaccharide of O139 and O-specific polysaccharide of LPS elicited vibriocidal antibodies in mice. Clinical trials of these conjugates are planned.