Bacterial meningitis is an acute infection of the fluid surrounding the brain and spinal cord that can rapidly lead to death. Capsular polysaccharides are a major virulence factor and form the basis for serogroup designation and protective vaccines. Polysaccharide vaccines have been replaced by glycoconjugate vaccines in order to improve the immunogenicity in infants and young children and inducing memory responses. The conjugates also induced high antibody avidity and prolong the IgG persistence. Moreover, compared with the polysaccharide vaccine, the conjugate vaccine can induce a long-lasting, protective memory T-cell response and elicit a comprehensive humoral and cellular immune response. In this study a new synthetic strategy was used to prepare two kinds of monovalent effective meningococcal vaccines. Group C and group W135 meningococcal capsular polysaccharide (GCMP and GWMP) were aldylated with sodium periodate, followed by the conjugation with tetanus toxoid (TT) via the heterotelechelic crosslinker N-β-maleimidopropionic acid hydrazide, separately. The BALB/c mice were immunized with the two conjugates. The polysaccharide (PS) specific antibody and the TT specific antibody in sera by indirect ELISA, and the avidity of PS specific antibody by thiocyanate elution were determined. The results showed that the mass ratios of PS to protein were 0.4 (GCMP-TT) and 1.0 (GWMP-TT). The PS specific antibody in GCMP-TT group were 3.2, 1.4 and 1.2 times, higher than those in GCMP group in primaty, 1st boost and 2nd boost, which were 2.5, 2.2 and 2.8 in GWMP-TT group, indicating the immune enhancement of both conjugate vaccines. The ratios of IgG2a to IgG1 were much higher in PS-TT groups than that in PS groups, demonstrated the conversion of TI antigen to TD type. The doubled avidity index of PS specific antibody in PS-TT groups showed the effective immune memory induced by the conjugation of carrier proteins to polysaccharides. This study confirmed that this synthetic route can effectively synthesize vaccines with better immunogenicity and improve the immune effect of the meningitis vaccine, and has a good application prospect.
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