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 1 studies confirmed the superior immunity of recombinant exoprotein A of Pseudomonas aeruginosa (rEPA) bound to Vi. Phase 2 and phase 3 studies with this investigational vaccine are planned 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-O-acetylated pectin as a vaccine for typhoid fever, is being prepared for clinical evaluation. Escherichia coli O157, considered as an important emerging pathogen in the U.S., causes hemolytic uremic syndrome in young children. Phase 1 study of the detoxified O-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 O-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. Poly(dA) has similar charge distribution as poly`(2-8) sialic acid, the capsular polysaccharide of group B meningococci. We conjugate poly(dA) with a carrier protein and mice immunized with poly(dA)-BSA conjugate elicited anti-sialic acid antibody. We showed for this a highly charged, flexible polymer, the charge distribution is the dominant factor for specificity.
