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目的优化C群脑膜炎球菌多糖-破伤风类毒素(Tetanus toxoid,TT)结合疫苗的制备工艺。方法分别采用衍化的降解多糖与TT结合、衍化TT与降解多糖结合和1-氰基-4-二甲基氨基吡啶.四氟化硼(CDAP)活化降解多糖后衍化再与TT结合的方法制备C群脑膜炎球菌多糖蛋白结合物PSAH-TT、PS-AHTT和PSCDAPAH-TT,并进行生化指标和抗原性检测,与溴化氰(CNBr)活化多糖衍化与TT的结合物PSCNBrAH-TT进行免疫原性比较,确定最适制备工艺,并制备2批结合疫苗,与市售疫苗进行免疫原性比较。结果 3种方法制备的多糖蛋白结合物生化指标存在差异,以PSCDAPAH-TT收率最高,且均保持了多糖的抗原性及免疫原性,并有免疫加强效应;PSCDAPAH-TT免疫2针后抗体GMT水平高于PSAH-TT和PS-AHTT,差异有统计学意义(P<0.05),3针后抗体GMT水平仍高于PSAH-TT和PS-AHTT,但差异无统计学意义(P>0.05),PSCDAPAH-TT免疫2针和3针后抗体GMT水平均高于PSCNBrAH-TT,且2针后差异有统计学意义(P<0.05),3针后差异也无统计学意义(P>0.05),但制备的2批PSCDAPAH-TT疫苗免疫2针和3针后的抗体GMT水平均明显高于市售疫苗,差异有统计学意义(P<0.05)。结论经CDAP活化降解多糖后衍化再与载体蛋白结合制备的疫苗具有较好的免疫原性。
Objective To optimize the preparation of C group meningococcal polysaccharide - tetanus toxoid (TT) conjugate vaccine. Methods The degenerative polysaccharides derived from dextran were respectively combined with TT to derivatize the combination of TT with degrading polysaccharides and 1-cyano-4-dimethylaminopyridine. Boron tetrafluoride (CDAP) C group meningococcal polysaccharide protein conjugates PSAH-TT, PS-AHTT and PSCDAPAH-TT, and biochemical and antigenic detection, and cyanogen bromide (CNBr) activated polysaccharide derivative and TT conjugate PSCNBrAH-TT were immunized Comparison of the origin, to determine the optimum preparation process, and preparation of two batches of conjugate vaccine, immunogenicity compared with the commercially available vaccine. Results The biochemical indexes of the polysaccharide conjugates prepared by the three methods were different. PSCDAPAH-TT had the highest yield, and both of them maintained the antigenicity and immunogenicity of the polysaccharide. The immune enhancement effect was also observed. PSCDAPAH-TT The level of GMT was higher than that of PSAH-TT and PS-AHTT (P <0.05), but the level of GMT was still higher than that of PSAH-TT and PS-AHTT after 3 doses ), PSGAPAH-TT immune 2-pin and 3-pin post-antibody GMT levels were higher than PSCNBrAH-TT, and 2-post difference was statistically significant (P <0.05), 3 needle after the difference was not statistically significant ). However, the GMT levels of the two batches of PSCDAPAH-TT vaccine immunized with 2 and 3 doses were significantly higher than those of the commercially available vaccine (P <0.05). Conclusion Vaccines prepared by CDAP activation-degradation of polysaccharides and then derivatized with carrier protein have good immunogenicity.