Fusion protein Ag85B-MPT64190-198-Mtb8.4 has higher immunogenicity than Ag85B with capacity to boost BCG-primed immunity against Mycobacterium tuberculosis in mice

被引:32
|
作者
Luo, Yu [1 ,2 ]
Wang, Bingxiang [3 ]
Hu, Lina [3 ]
Yu, Hongjuan [1 ,2 ]
Da, Zejiao [1 ,2 ]
Jiang, Wenwen [1 ,2 ]
Song, Nannan [1 ,2 ]
Qie, Yaqing [4 ]
Wang, Honghai [4 ]
Tang, Zhijiao [5 ]
Xian, Qiaoyang [5 ]
Zhang, Ying [1 ,2 ,6 ]
Zhu, Bingdong [1 ,2 ]
机构
[1] Lanzhou Univ, Sch Basic Med Sci, Inst Pathogen Biol, Lanzhou 730000, Peoples R China
[2] Lanzhou Univ, Sch Basic Med Sci, Lanzhou Ctr TB Res, Lanzhou 730000, Peoples R China
[3] Lanzhou Inst Biol Prod, Lanzhou, Peoples R China
[4] Fudan Univ, Inst Genet, Shanghai, Peoples R China
[5] Wuhan Univ, ABSL Lab 3, Wuhan, Peoples R China
[6] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA
基金
国家高技术研究发展计划(863计划);
关键词
Mycobacterium tuberculosis; Subunit vaccine; Fusion protein; BCG; Polysaccharide nucleic acid adjuvant; Prime-boost;
D O I
10.1016/j.vaccine.2009.08.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tuberculosis (TB) remains a major infectious disease worldwide despite chemotherapy and BCG vaccine. The efficacy of the current TB vaccine BCG varies from 0 to 80%. New vaccines that have better protection than BCG or have the capability to boost BCG-primed immunity are urgently needed. We have previously constructed a fusion protein Ag85B-MPr64(190-198)-Mtb8.4 (AMM). In this study, we investigated the immunogenicity of the fusion protein AMM in a novel adjuvant of dimethyl-dioctyldecyl ammonium bromide and BCG polysaccharide nucleic acid (DDA-BCG PSN), and its capacity to boost BCG-primed immunity. The anti-Ag85B antibodies IgG1 and IgG2a were determined using ELISA and the number of spleen cells secreting IFN-gamma was determined by ELISPOT. In addition, the ability of the subunit vaccine AMM to boost BCG-primed immunity against Mycobacterium tuberculosis was analyzed. The fusion protein AMM induced more effective humoral and cell-mediated immune responses in mice than Ag85B alone. Mice primed with BCG vaccination followed by boosting with AMM produced a stronger immune response and afforded a better protection against M. tuberculosis infection than mice immunized with BCG alone or BCG priming followed by boosting with Ag85B. These findings suggest that AMM is a promising candidate subunit vaccine to enhance the protective efficiency of BCG. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6179 / 6185
页数:7
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