Comparative immunogenicities of Vi polysaccharide-protein conjugates composed of cholera toxin or its B subunit as a carrier bound to high- or lower-molecular-weight Vi

Abstract

The effect of molecular weight or size of the components on the immunogenicity of polysaccharide-protein conjugates prepared with the native Vi capsular polysaccharide (Vi) (approximately 3 x 10(3) kilodaltons) or lower-molecular-weight Vi (Vis; approximately 46 kilodaltons) abound to cholera toxin (CT) or to its B subunit (CTB) was studied. In mice, Vi-CT, Vi-CTB, and Vis-CTB elicited higher Vi antibody levels than the Vi alone (P less than 0.0001). Vi-CT and Vi-CTB were more immunogenic than Vis-CTB (P less than 0.01). CT or Vi-CT elicited higher levels of CT antibodies, as measured by enzyme-linked immunosorbent assay, than did CTB or Vi-CTB. In rhesus monkeys, the Vi conjugates elicited higher Vi antibody levels than the Vi alone (P less than 0.01). Vi-CTB elicited higher levels of Vi antibody after each injection than did Vis-CTB. Similar levels of CT antibodies, as measured by enzyme-linked immunosorbent assay, were elicited by all three conjugates. In contrast, Vi-CT elicited higher levels of neutralizing antibodies than Vi-CTB or Vis-CTB when either CT or the related heat-labile toxin of Escherichia coli was used as the antigen. These results indicate that the holotoxin and the native Vi provide the most immunogenic components for conjugates designed to induce both Vi and CT antibodies.