分枝杆菌脂质组分加强结核分枝杆菌亚单位疫苗效应的初步研究

何珊珊1,2,何娟娟1,3,刘勋1,3,孔祥熙1,2,谭继英1,2,祝秉东1,3

微生物与感染 ›› 2015, Vol. 10 ›› Issue (4) : 228-234.

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微生物与感染 ›› 2015, Vol. 10 ›› Issue (4) : 228-234.
论著

分枝杆菌脂质组分加强结核分枝杆菌亚单位疫苗效应的初步研究

  • 何珊珊1,2,何娟娟1,3,刘勋1,3,孔祥熙1,2,谭继英1,2,祝秉东1,3
作者信息 +

Mycobacterium lipid components enhanced the protective efficacy of tuberculosis subunit vaccine

  • HE Shan-Shan1,2,HE Juan-Juan1,3,LIU Xun1,3,KONG Xiang-Xi 1,2,TAN Ji-Ying1,2,ZHU Bing-Dong1,3
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摘要

分枝杆菌细胞壁含丰富的脂质组分,其中一些具有抗原性,或具有重要的免疫调节作用。为探讨这些脂质组分在结核分枝杆菌亚单位疫苗中的作用,研发有效疫苗,本研究对卡介苗(BCG)细胞壁总脂成分进行萃取,用硅胶柱色谱法将其分离为非极性脂、中间极性脂和极性脂,检测各类脂质组分在人群中的免疫原性,并将总脂和各类脂质组分分别与佐剂二甲基三十六烷基铵(DDA)和Poly(I:C)混合,进一步与结核分枝杆菌融合蛋白LT70(ESAT6­-Ag85B­-MPT64<190­-198>­Mtb8.4­Rv2626c)混合,构建含脂质的结核分枝杆菌亚单位疫苗。在小鼠BCG攻击模型中进行保护效率评价,包括BCG初免后含脂质亚单位疫苗的强化免疫保护效率评价。结果显示,结核病患者脂质特异性抗体IgG高于健康人群(P<0.05)。在小鼠BCG攻击模型免疫保护效果评价中,含脂质亚单位疫苗LT70­总脂组小鼠肺部的荷菌数显著低于BCG组(P<0.05)。在BCG初免­含脂质亚单位疫苗加强免疫策略中,LT70­总脂和LT70­中间极性脂组小鼠肺部荷菌数均低于BCG组(P<0.01)和LT70组(P<0.05)。研究表明,分枝杆菌脂质成分具有较强的免疫原性,与亚单位疫苗联合使用能增强亚单位疫苗的抗结核分枝杆菌效果。其中,中间极性脂类强化作用明显,值得深入研究。

Abstract

Mycobacterium cell wall is rich in lipid components, and some of the lipids may have antigenicity or play an important role in the process of immune regulation. To investigate the effects of the lipids from Mycobacterium cell wall in tuberculosis subunit vaccine, the total lipids were extracted from bacillus Calmette­Guérin (BCG) cell wall and separated by silica column into three different groups: the nonpolar lipids, the intermediate polar lipids and the polar lipids. The lipids were used as the antigen to screen the immune responses in general population. Furthermore, the total lipids and the three groups of lipids were mixed with fusion protein LT70(ESAT6­-Ag85B­MPT64<190­1-98>­Mtb8.4­-Rv2626c) in adjuvant of N, N′­dimethyl­N, N′­dioctadecylammonium(DDA) and Poly (I:C) respectively. The subunit vaccines containing lipids were used to immunize mice and the protective efficacy were evaluated by challenging with BCG. The results showed that the level of lipid­specific IgG in tuberculosis patients was significantly higher than that in healthy people (P0.05). For the protective efficacy, the number of bacteria harbored in mice immunized with LT70­total lipids significantly declined compared with BCG vaccination (P0.05). In BCG prime­subunit vaccine boost strategy, LT70­total lipids and LT70­intermediate polar lipids vaccines resulted in significantly low bacterial number than BCG (P0.01) and LT70 (P0.05). In conclusion, lipids from Mycobacterium cell wall have high immunogenicity; combination of them, especially the total lipids or intermediate polar lipids, with fusion protein antigen can enhance the antimycobacterial protective efficacy of subunit vaccine.

关键词

结核分枝杆菌 / 亚单位疫苗 / 卡介苗 / 细胞壁 / 脂质

Key words

Mycobacterium tuberculosis / Subunit vaccine / Bacillus Calmette-Guérin / Cell wall envelope / Lipid

引用本文

导出引用
何珊珊1,2,何娟娟1,3,刘勋1,3,孔祥熙1,2,谭继英1,2,祝秉东1,3. 分枝杆菌脂质组分加强结核分枝杆菌亚单位疫苗效应的初步研究[J]. 微生物与感染. 2015, 10(4): 228-234
HE Shan-Shan1,2,HE Juan-Juan1,3,LIU Xun1,3,KONG Xiang-Xi 1,2,TAN Ji-Ying1,2,ZHU Bing-Dong1,3. Mycobacterium lipid components enhanced the protective efficacy of tuberculosis subunit vaccine[J]. Journal of Microbes and Infections. 2015, 10(4): 228-234

基金

“十二五”国家科技重大专项(2012ZX10003--008--006)


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