Synthesis and immunogenicity in mice of conjugate vaccine of Salmonella paratyphi A O-SP bound to Tetanus toxoid

To develop polysaccharide-protein conjugate vaccine for proventing Salmonella paratyphi A infection. Salmonella paratyphi A NTP-6 strain was fermented, then LPS was extracted with hot-phenyl method and detoxificated with 1% acetic acid at 100℃ for 1.5 h; the O-SP mixture was purified with Sephadex G-75, and the first and second peak were collected as effective polysaccharide antigen. O-SP was activated with CDAP, bound to TT with ADH as a spacer, and condensed with EDAC. Solutions of 2.5 mu-g of saccharide, alone or as conjugate, were injected subcutaneous into young mice. Antibodies against LPS in serum of the mice were measured by ELISA. Complement-mediated bactericidal activity was also assayed. The safety of conjugate vaccine was evaluated in mice and guinea pig. After the second injection, the mean geometric titer （GMT） of anti-LPS IgG increased by more than 4 times, and the third injection showed significantly booster response. In the complement-mediated bactericidal activity test, the titers of antiserum were above 1:1280. In mice and guinea pig, conjugate vaccine had not shown any harmful effect. A Salmonella paratyphi A conjugate vaccine preparation procedure was succesfully constructed. The TI antigen of O-SP was effectively converted into TD antigen; Clinical evaluation of S. paratyphi A conjugate vaccine is planned.