Preliminary Studies On Experimental Typhoid Vi Polysaccharide Conjugate Vaccine

The Vi polysaccharide of Typhoid is a licensed vaccine for Typhoid Fever in individuals ≥5 years old in China. One injection of Vi polysaccharide of Typhoid only offered about 70% protective efficacy. Moreover it only elicited low and short-lived level of serum antibodies in children 2-5 years old, and could not induce protective level of serum antibodies in children below 2 years old, Rejection does not elicit a boost response at any age.To improve the immunogenicity of Typhoid Vi polysaccharide, at first Vi polysaccharide was activated by CNBr and 1-cayno-dimethylamino pyridinium tetrafluoroborate (CDAP) and then linked with adipic acid dihydrazide (ADH) to synthesize ADH derivatives of Vi polysaccharide (Vi-AH). But no Vi-AH was found. It showed that CNBr and CDAP were not available for Vi polysaccharide conjugate. With 1-ethyl-N- (3-dimethylaminoprpyl) -carbodiimide(EDAC), Vi polysaccharide conjugate (Vi-TT) can be synthesized by Vi polysaccharide of Typhoid directly bounded to Tetanus toxoid (TT). The second strategy was that TT was first treated with ADH and ED AC to form ADH derivatives of TT (TT-AH), then TT-AH was connected with Typhoid Vi polysaccharide to synthesize Vi polysaccharide conjugate (TT-AH-Vi), The third strategy was that Vi polysaccharide of Typhoid was first treated with ADH and ED AC to form Vi-AH, then Vi-AH was conjugated with TT to synthesize Vi polysaccharide conjugate (Vi-AH-TT). Vi polysaccharide conjugates were synthesized by three methodsabove. The immunogenicity of these Vi polysaccharide conjugates in mice was analyzed.Results showed that all Vi polysaccharide conjugates could elicit significantly higher anti-Vi IgG levels than Vi polysaccharide of Typhoid alone after third injections. TT-AH-Vi, conjugate had the best imrnunogenicity. The anti-Vi IgG GMT of TT-HA-Vi came up to 735.17 and significantly differed from that of Vi-TT and Vi-AH-TT conjugates. After the first injection, TT-AH-Vi,, TT-AH-Vi₂ and TT-AH-Vi₃ all elicited significantly higher anti-Vi IgG than Vi polysaccharide of Typhoid alone. After the second injection, they elicited significantly higher anti-Vi IgG levels than the first injection. After the third injection, the antibody responses of TT-AH-Vi conjugates were different from each other. The anti-Vi IgG GMT of TT-AH-Vi₁, and TT-AH- Vi₂ were higher than that of the second injection, only TT-AH-Vi₂ having significant difference. The anti-Vi IgG GMT of TT-AH-Vi₃ was lower than that of the second injection, but having no significant difference. It was concluded that Vi polysaccharide of Typhoid, conjugated with TT, could significantly improve its immunogenicity.