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
相关论文
共 42 条
  • [1] Evaluation of a new recombinant BCG which contains mycobacterial antigen ag85B-mpt64190-198-mtb8.4 in C57/BL6 mice
    Qie, Y. Q.
    Wang, J. L.
    Zhu, B. D.
    Xu, Y.
    Wang, Q. Z.
    Chen, J. Z.
    Wang, H. H.
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2008, 67 (02) : 133 - 139
  • [2] Immunogenicity and Protective Efficacy of a Fusion Protein Vaccine Consisting of Antigen Ag85B and HspX against Mycobacterium tuberculosis Infection in Mice
    Li, Q.
    Yu, H.
    Zhang, Y.
    Wang, B.
    Jiang, W.
    Da, Z.
    Xian, Q.
    Wang, Y.
    Liu, X.
    Zhu, B.
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2011, 73 (06) : 568 - 576
  • [3] More Vaccine Efficacy Studies on the Recombinant Bacille Calmette-Guerin Co-expressing Ag85B, Mpt64190-198 and Mtb8.4
    Qie, Y. Q.
    Wang, J. L.
    Liu, W.
    Shen, H.
    Chen, J. Z.
    Zhu, B. D.
    Xu, Y.
    Zhang, X. L.
    Wang, H. H.
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2009, 69 (04) : 342 - 350
  • [4] Comparative evaluation of booster efficacies of BCG, Ag85B, and Ag85B peptides based vaccines to boost BCG induced immunity in BALB/c mice: a pilot study
    Husain, Aliabbas A.
    Warke, Shubhangi R.
    Kalorey, Dewanand R.
    Daginawala, Hatim F.
    Taori, Girdhar M.
    Kashyap, Rajpal S.
    CLINICAL AND EXPERIMENTAL VACCINE RESEARCH, 2015, 4 (01) : 83 - 87
  • [5] Heterologous Prime Boost Regimes with N-terminal Peptides of Ag85B Induces Better Protection than Ag85B and BCG in Murine Model of Tuberculosis
    Husain, Aliabbas A.
    Daginawala, Hatim F.
    Warke, Shubhangi R.
    Kalorey, Dewanand R.
    Kurkure, Nitin V.
    Nayak, Amit R.
    Purohit, Hemant J.
    Taori, Girdhar M.
    Kashyap, Rajpal S.
    INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, 2016, 22 (01) : 143 - 153
  • [6] Heterologous Prime Boost Regimes with N-terminal Peptides of Ag85B Induces Better Protection than Ag85B and BCG in Murine Model of Tuberculosis
    Aliabbas A. Husain
    Hatim F. Daginawala
    Shubhangi R. Warke
    Dewanand R. Kalorey
    Nitin V. Kurkure
    Amit R. Nayak
    Hemant J. Purohit
    Girdhar M. Taori
    Rajpal S. Kashyap
    International Journal of Peptide Research and Therapeutics, 2016, 22 : 143 - 153
  • [7] Enhancement of Ag85B DNA vaccine immunogenicity against tuberculosis by dissolving microneedles in mice
    Yan, Qinying
    Chen, Zhigang
    Liu, Houming
    Shan, Wanshui
    Cheng, Zhide
    Dai, Xuyong
    Xue, Yun
    Chen, Fan
    VACCINE, 2018, 36 (30) : 4471 - 4476
  • [8] Chimaeric protein improved immunogenicity compared with fusion protein of Ag85B and ESAT-6 antigens of Mycobacterium tuberculosis
    Xu, Y.
    Wang, B.
    Chen, J.
    Wang, Q.
    Zhu, B.
    Shen, H.
    Qie, Y.
    Wang, J.
    Wang, H.
    SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2006, 64 (05) : 476 - 481
  • [9] The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol Mycobacterium tuberculosis infection
    Prendergast, K.
    Counoupas, C.
    Triccas, J.
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2016, 46 : 604 - 604
  • [10] The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol Mycobacterium tuberculosis infection
    Prendergast, Kelly A.
    Counoupas, Claudio
    Leotta, Lisa
    Eto, Carolina
    Bitter, Wilbert
    Winter, Nathalie
    Triccas, James A.
    VACCINE, 2016, 34 (23) : 2608 - 2615