佐剂DDA和MPL对提高结核杆菌组合DNA疫苗免疫效果的比较研究  

DDA is More Efficacious Than MPL as Adjuvants That Enhanced Immunogenicity and Protection of Combined DNA Vaccine Against Mycobacterium tuberculosisa

作　　者：余大海[1] 蔡宏[1] 朱玉贤[1] 

机构地区：[1]北京大学蛋白质工程及植物基因工程国家重点实验室,北京100871

出　　处：《生物化学与生物物理进展》2005年第8期765-770,共6页Progress In Biochemistry and Biophysics

基　　金：国家高技术"863"计划资助项目(2002AA206411)~~

摘　　要：编码结核杆菌3种抗原Ag85B,MPT64,MPT83的基因片段插入真核表达载体作为组合疫苗免疫小鼠,DDA和MPL作为佐剂分别提高了此三价苗的免疫原性和免疫保护效果,且相比之下DDA优于MPL.添加DDA后,Ag85B,MPT64,MPT83抗原特异的IFN-γ含量分别为(265.37±79.2)U/ml,(185.31±58.3)U/ml,(108.13±54.4)U/ml,分别比非佐剂组的高16U/ml,45U/ml和2U/ml,与MPL组3种抗原特异性IFN-γ的含量无显著差异.IL-4的含量在各组中无显著差异.攻毒后细菌计数结果显示,添加佐剂的三价苗组小鼠的肺脏和脾脏的载菌量分别比空载体组降低了2￣3个数量级,且佐剂DDA组显著优于佐剂MPL组和未加佐剂组.病理切片结果与载菌量数据相一致,添加佐剂组,特别是DDA组小鼠肺部淋巴细胞相对减少,巨噬细胞增多.因此,DDA作为佐剂能显著提高核酸疫苗的免疫效率,佐剂MPL不能提高结核杆菌多价核酸疫苗的免疫效率.Combined DNA vaccine encoding Ag85B, MPT64 and MPT83 of Mycobacterium tuberculosis were formulated into DDA and MPL to immunize mice and then the immunogenicity and protective efficacy of each group were evaluated. The DDA and MPL groups induced a much more enhanced Thl-type cellular response indicated by the higher levels of IFN-γ compared with that without any adjuvant. In DDA group, antigens specific IFN-γ for Ag85B, MPT64, MPT83 are （265.37±79.2） U/ml, （185.31±58.3） U/ml, （108.13±54.4） U/ml respectively which are 16 U/ml, 45 U/ml, 2 U/ml higher than that of the non-adjuvant group. The bacterial CFU in lungs and spleens of the DDA group was reduced 1/5 and 1/4 respectively relative to the same combined vaccine with MPL and without adjubvants. The pathological lungs slices of adjuvant groups gave consistent result that showed less damage than non-adjuvant group due to influx of epithelioid macrophages and less neutrophils. In conclusion, DDA is more efficacious than MPL as adjuvants to enhance immune efficacy of combined DNA vaccine in mice.

关 键 词：结核分支杆菌 组合疫苗 佐剂 DDA MPL 免疫效果 

分 类 号：S855.2[农业科学—临床兽医学]