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

来源：

VACCINE | 2009年 / 27卷 / 44期

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

页码：6179 / 6185

页数：7

共 42 条

[41] Subcutaneous Administration of Modified Vaccinia Virus Ankara Expressing an Ag85B-ESAT6 Fusion Protein, but Not an Adenovirus-Based Vaccine, Protects Mice Against Intravenous Challenge with Mycobacterium tuberculosis
You, Q.
Jiang, C.
Wu, Y.
Yu, X.
Chen, Y.
Zhang, X.
Wei, W.
Wang, Y.
Tang, Z.
Jiang, D.
Wu, Y.
Wang, C.
Meng, X.
Zhao, X.
Kong, W.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2012, 75 (01) : 77 - 84
[42] Protection against tuberculosis induced by oral prime with Mycobacterium bovis BCG and intranasal subunit boost based on the vaccine candidate Ag85B-ESAT-6 does not correlate with circulating IFN-γ producing T-cells
Badell, Edgar
Nicolle, Fabienne
Clark, Simon
Majlessi, Laleh
Boudou, Frederic
Martino, Angelo
Castello-Branco, Luiz
Leclerc, Claude
Lewis, David J. M.
Marsh, Philip D.
Gicquel, Brigitte
Winter, Nathalie
VACCINE, 2009, 27 (01) : 28 - 37

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