摘要
目的研究C群脑膜炎球菌荚膜多糖(Group C meningococcal polysaccharide,GCMP)与破伤风类毒素(Tetanustoxoid,TT)结合疫苗的工艺稳定性及其免疫原性。方法以己二酸二酰肼(ADH)作为间隔剂,碳二亚胺(EDAC)为缩合剂,扩大量制备8批GCMP-TT结合物,以生化、免疫学方法分析8批GCMP-AH衍生物和GCMP-TT结合物的主要特性;将8批GCMP-TT结合物分别免疫NIH小鼠,ELISA法检测小鼠血清中特异性抗GCMP和抗TT的IgG抗体,分析其免疫原性。结果 8批GCMP-AH衍生物及GCMP-TT结合物各项生化检测指标基本一致,批间差异较小,均达到《欧洲药典》的规程(7.0版)要求,并具有良好的抗原性。免疫小鼠的血清中均产生了较高水平的抗GCMP和抗TT的特异性IgG抗体,与GCMP产生的特异性IgG抗体相比,差异有统计学意义(P<0.001);GCMP-TT结合疫苗第2针、第3针与第1针相比,免疫后产生的IgG抗体水平差异均有统计学意义(P<0.001)。结论 GCMP-TT结合疫苗的制备工艺稳定、可靠,具有良好的免疫原性,并可诱导免疫记忆,为脑膜炎球菌结合疫苗的规模化生产提供了重要的实验依据。
Objective To investigate the technological stability and immunogenicity of group C meningococcal polysaccharidetetanus toxoid（GCMP-TT） conjugate vaccine.Methods Eight batches of GCMP-TT conjugates were prepared on a large scale by using adipic dihydrazide（ADH）as the spacer and 1-ethyl-3（-3-dimethylaminopmpyl）carbodiimide（EDAC）as the coupling agent.The main characteristics of GCMP-AH derivatives and GCMP-TT conjugates were assessed by biochemical and immunological assays.NIH mice were immunized with the 8 batches of conjugates respectively,and determined for specific IgGs against GCMP and TT in sera by ELISA to evaluate the immunogenicity.Results All the 8 batches of GCMP-AH derivatives and GCMP-TT conjugates showed high antigenicities,of which the biochemical indexes were basically in agreement with little difference between batches,and met the requirements in European Pharmacopoeia（7th Edition）.High specific IgG titers against GCMP and TT were elicited in sera of immunized mice,which showed significant difference with those elicited by CGMP（P 〈 0.001）.The IgG levels elicited after the 2nd and 3rd doses of GCMP-TT conjugates were significantly higher than that by the 1st dose（P 〈 0.001）.Conclusion The production procedure of GCMP-TT conjugate was stable and reliable,and the prepared conjugates showed high immunogenicity,which provided an important basis for large scale production of meningococcal conjugate vaccines.
出处
《中国生物制品学杂志》
CAS
CSCD
2012年第8期933-938,共6页
Chinese Journal of Biologicals
基金
2008年甘肃省重大科技专项资助项目(0801NKDA003)
关键词
C群脑膜炎球菌多糖
结合疫苗
制备工艺
稳定性
免疫原性
Group C meningococcal polysaccharide； Conjugate vaccine； Preparation technology； Stability； Immunogenicity
