Serum antibodies to the surface polysaccharides of Gram-negative enteric bacteria confer protective immunity against these pathogens. Vi capsular polysaccharide of Salmonella typhi was conjugated with protein to improve its immunogenicity. Phase I studies confirmed the superior immunity of recombinant exoprotein A of Pseudomonas aeruginosa (rEPA) bound to Vi. A phase 2 study with this investigational vaccine has been completed for Vietnam, an area with a high attack rate of typhoid fever. A semi- synthetic Vi antigen using plant polysaccharide. pectin, was prepared and showed identical antigenicity as the native Vi. A conjugate, composed of a di-0-acetylated pectin as a vaccine for typhoid fever, has been prepared for a phase l study in Vietnam for comparative immunogenicity with Vi conjugates. A different synthetic scheme for preparing Vi conjugates was devisednd the new product characterized for its immunogenicity in mice. Escherichia coli 0-157, considered as an important emerging pathogen in the U.S., causes hemolytic uremic syndrome in young children. Phase 1 study of the detoxified 0-specific polysaccharide and covalently bound to rEPA elicited 100-fold antibody rise in healthy adults after four weeks and the antibodies were bactericidal. We plan a phase 2 study for therapeutic usage of hyperimmune plasma in children. Salmonella paratyphi A accounts for 10% of enteric fever in Southeast Asia. A vaccine prepare in the similar fashion as E. coli 0-157 was prepared and elicited bactericidal antibodies in mice. We plan to use this conjugate as a control in our phase 2 study in Vietnam.
