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 polysaccharide was 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 surveillance. Salmonella paratyphi A, the second most common cause of enteric fever in Southeast Asia, were 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 children 2-5 year olds is planned. Non-toxic shiga toxin I are purified from mutant E. coli O157 and to be conjugated with O-specific polysaccharide for a bivalent vaccine. The major reservoir of E.coli O157 is cattle. LPS and O-specific polysaccharide conjugate showed to be immunogenic in 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 elicited vibriocidal antibodies in mice. Clinical trials of these conjugates are planned.
