Synthesis and immunogenicity in mice of conjugate vaccine of Salmonella paratyphi A O--SP bound to Tetanus toxoid
Objective To develop polysaccharide-protein conjugate vaccine for proventing Salmonella paratyphi A infection.Methods Salmonella paratyphi A NTP-6 strain was fermented,then LPS was extracted with bot-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 polysaceharide antigen.O-SP was activated with CDAP,bound to TT with ADH as a spacer,and condensed with EDAC.Solutions of 2.5μg of sac- charide,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 con- jugate vaccine was evaluated in mice and guinea pig.Results After the second injection,the mean geometric titer (GMT)of anfi-LPS IgG increased by mere than 4 times,and the third injection showed significantly booster re- sponse.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.Conclusion A Salmonella paratyphi A con- jugate vaccine preparation procedure was successfully constructed.The TI antigen of O-SP was effectively converted into TD antigen; Clinical evaluation of S.paratyphi A conjugate vaccine is planned.