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（DT）结合疫苗，再配比制成ACYW135群脑膜炎球菌多糖结合疫苗（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ACYW135-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。

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.