不同蛋白载体制备A、C、Y、W_(135)群四价脑膜炎球菌多糖结合疫苗的免疫原性  

Immunogenicity of groups A,C,Y and W_(135) meningococcal polysaccharide conjugate vaccines prepared with various protein carriers

作　　者：佟巍[1] 孙晓东[1] 刘建斌 尹珊珊[1] 刘建凯[1] 

机构地区：[1]北京民海生物科技有限公司,北京102600

出　　处：《中国生物制品学杂志》2018年第2期121-124,128,共5页Chinese Journal of Biologicals

基　　金："重大新药创制"重大科技专项十二五课题(2014ZX9102041001)

摘　　要：目的探讨以破伤风类毒素(tetanus toxoid,TT)及白喉类毒素(diphtheria toxoid,DT)为载体的A、C、Y、W_(135)群四价脑膜炎球菌多糖结合疫苗的免疫原性。方法将A、C、Y、W_(135)群流脑多糖经溴化氰(CNBr)活化后,以1,6己二酰肼(1,6-adipic acid dihydrazide,ADH)作为衍生剂制备相应的衍生物,分别与TT及DT在碳二亚胺[N-(3-Dimethylami-nopropyl)-N’-ethylcarbodiimide hydrochloride,EDAC]作用下结合,经Sepharose 4FF凝胶层析纯化后,加入冻干保护剂进行冻干,制备成A、C、Y、W_(135)群四价脑膜炎球菌多糖结合疫苗。用两种蛋白载体疫苗分别按1及2.5μg两个剂量(各型多糖的含量为1和2.5μg)免疫小鼠,经腹部皮下注射,于0及14 d各免疫1次,于首次免疫后第28天经静脉采血,分离血清,ELISA法检测血清各型抗体水平。结果 1及2.5μg两个剂量组的阳转率均高于80%,2.5μg免疫组的阳转率优于1μg免疫组;总体上来说,以TT为蛋白载体结合疫苗的阳转率高于以DT为载体的结合疫苗,对A和W_(135)群脑膜炎球菌多糖结合疫苗较明显。结论以TT及DT为载体制备的A、C、Y、W_(135)群四价脑膜炎球菌多糖结合疫苗均具有良好的免疫原性,TT略优于DT。Objective To investigate the immunogenicity of groupsA, C, Y and W135 meningococcal polysaccharide conjugate vaccines prepared with various protein carriers （tetanus toxoid and diphtheria toxoid）. Methods Groups A, C, Y and Wl35 meningococeal polysaeeharide were activated with cyanogens bromide （CNBr） and prepared into poiysaccharide derivatives using 1, 6-adipic acid dihydrazine （ADH） as a derivating agent, then combined with purified tetanus toxoid （TF） and diphtheria toxoid （DT） respectively in mediation of 1-ethyl-3 （3-dimethylaminopropyl）- carbodiimide （EDAC）, purified by Sepharose 4FF chromatography and added with stabilizer to prepare MenAps-TT, MenCps-Tl＇, MenYps-TY, MenWps-TF, MenAps-DT, MenCps-DT, MenYps-DT and MenWps-DT conjugate vaccines. Mice were immunized s.c. with the vaccines at dosages of 1 and 2. 5 μg （contents of polysaccharides of various types） separately on days 0 and 14, of which the serum samples were collected on day 28 after the first immunization and ,letermined for antibody titer by ELISA to calculate the antibody positive conversion rate. Results The positive onversion rates induced by the vaccines at dosages of 1 and 2. 5 μg were more than 80%, which were higher in the mice immunized with 2. 5 μg of vaccines than in those with 1 μg. In general, the positive rates induced by the vaccines using TF as protein carrier were higher than those using DT, especially those by groups A and W135 meningococcal polysaccharide conjugate vaccines.

关 键 词：脑膜炎球菌多糖结合疫苗 蛋白载体 破伤风类毒素 白喉类毒素 免疫原性 

分 类 号：R378.15[医药卫生—病原生物学] R392.33[医药卫生—基础医学]