ACYW135群脑膜炎球菌多糖结合疫苗的研制

摘要

Objective To prepare a safe and effective quadrivalent meningococcal polysaccharide conjugate vaccine.Methods Groups A,C,Y and W135 meningococcal polysaccharide were activated by cyanogen bromide,respectively.With 1,6-adipic acid dihydrazide as linking agent,monovalent meningococcal polysaccharide conjugate vaccines were prepared by carbodiimide-mediated coupling of meningococcal polysaccharide with carrier protein diphtheria toxoid (DT),then groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine (ACYW135-DT) was prepared by mixing each monovalent meningococcal polysaccharide conjugate vaccine in a certain proportion.Mice were immunized with ACYW135-DT,and antibodies to each polysaccharide were detected by indirect ELISA.The statistical analysis of the results were made by t test.Results Each index of the prepared ACYW135-DT achieved quality control standard.ACYW135-DT had a good safety and immunogenicity.The levels of IgG antibodies to group A (t =24.487,P＜0.01),group C (t =17.056,P ＜0.01),group Y (t =26.213,P ＜0.01) and group W135 (t =17.392,P ＜0.01) polysaccharides in mice immunized with ACYW135-DT were significantly higher than those in mice immunized quadrivalent meningococcal polysaccharide vaccine.Conclusion ACYW135-DT is successfully prepared with this technology.%目的 制备安全有效的四价脑膜炎球菌多糖结合疫苗.方法 用溴化氰分别将A、C、Y、W135群脑膜炎球菌多糖活化,以己二酸二酰肼作为连接剂,碳化二亚胺作为偶联剂,先制备单价A、C、Y、W135群脑膜炎球菌多糖-白喉类毒素(diphtheria toxoid,DT)结合疫苗,再配比制成ACYW135群脑膜炎球菌多糖结合疫苗(groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine,ACYW135-DT).以ACYW135-DT免疫小鼠,用间接ELISA检测小鼠血清抗各多糖抗体,采用t检验对检测结果进行统计学分析.结果 制备的ACYW135-DT的各项指标均达到质控标准,而且ACYW 135-DT具有良好的安全性和免疫原性,ACYW135-DT免疫小鼠的抗A群多糖-IgG(t=24.487,P＜0.01)、抗C群多糖-IgG(t=17.056,P＜0.01)、抗Y群多糖-IgG(t=26.213,P＜0.01)和抗W135群多糖-IgG(t=17.392,P＜0.01)水平明显高于四价脑膜炎球菌多糖疫苗免疫小鼠.结论 采用此项技术可成功制备ACYW135-DT.