LABORATORY AND PRELIMINARY CLINICAL CHARACTERIZATION OF VI CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

To improve its immunogenicity for children and adults and to make it s uitable for routine immunization of infants against typhoid fever, the capsular polysaccharide of Salmonella typhi (Vi) was bound to the B s ubunit of the heat-labile toxin (LT-B) of Escherichia coli or the reco mbinant exoprotein ii (rEPA) of Pseudomonas aeruginosa. The conjugates elicited higher levels of antibodies (micrograms per milliliter of se rum) in mice and in guinea pigs than did Vi and, unlike Vi alone, elic ited booster antibody responses in both species. In adult volunteers, Vi-LT-B and Vi-rEPA respectively, elicited higher levels of antibodies than Vi alone after the first injection (4.74 versus 1.77 and 4.91 ve rsus 1.77; P < 0.005) and 26 weeks later (2.32 and 2.69 versus 0.54; P < 0.04); a second injection of the conjugates did not elicit a booste r response of Vi antibodies. None of the 51 vaccinees had fever or sig nificant local reactions. Vi-rEPA elicited slightly higher levels of V i antibodies than did Vi-LT-B at II intervals after injection, but the se differences were not significant. Each conjugate elicited antibodie s to its carrier protein. The antibody responses elicited in adults by Vi bound to LT-B and rEPA are similar to those of other polysaccharid e-protein conjugates. These conjugates promise to be an improved Vi va ccine. Studies of Vi conjugates with adults and infants in areas where typhoid is endemic are planned.