A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Mycobacterium tuberculosis Induces Protective Immune Responses in M. tuberculosis H37Ra Infected Mice

被引:7
作者
Wang, Juan [1 ]
Xie, Tao [1 ]
Ullah, Inayat [1 ]
Mi, Youjun [1 ,2 ]
Li, Xiaoping [3 ]
Gong, Yang [1 ]
He, Pu [1 ]
Liu, Yuqi [1 ]
Li, Fei [1 ]
Li, Jixi [4 ]
Lu, Zengjun [5 ,6 ]
Zhu, Bingdong [1 ,6 ]
机构
[1] Lanzhou Univ, Sch Basic Med Sci, Inst Pathogen Biol, Gansu Prov Key Lab Evidence Based Med & Clin Trans, Lanzhou 730000, Peoples R China
[2] Lanzhou Univ, Sch Basic Med Sci, Inst Pathogen Physiol, Lanzhou 730000, Peoples R China
[3] Lanzhou Pulm Hosp, Resp Dept, Lanzhou 730000, Peoples R China
[4] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China
[5] Chinese Acad Agr Sci, Lanzhou Vet Res Inst, Lanzhou 730000, Peoples R China
[6] Lanzhou Univ, Coll Vet Med, State Key Lab Anim Dis Control & Prevent, Lanzhou 730000, Peoples R China
关键词
Mycobacterium tuberculosis; virus-like particles; subunit vaccine; Heparin-binding hemagglutinin; Mycobacterium tuberculosis pili; HEPARIN-BINDING HEMAGGLUTININ; VIRUS-LIKE PARTICLES; CELL-MEDIATED-IMMUNITY; INTERFERON-GAMMA; DENDRITIC CELLS; T-CELLS; PILI; GENERATION; CYTOKINES; ANTIBODY;
D O I
10.3390/vaccines11050941
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Heparin-binding hemagglutinin (HBHA) and M. tuberculosis pili (MTP) are important antigens on the surface of Mycobacterium tuberculosis. To display these antigens effectively, the fusion protein HBHA-MTP with a molecular weight of 20 kD (L20) was inserted into the receptor-binding hemagglutinin (HA) fragment of influenza virus and was expressed along with matrix protein M1 in Sf9 insect cells to generate influenza virus-like particles (LV20 in short). The results showed that the insertion of L20 into the envelope of the influenza virus did not affect the self-assembly and morphology of LV20 VLPs. The expression of L20 was successfully verified by transmission electron microscopy. Importantly, it did not interfere with the immunogenicity reactivity of LV20 VLPs. We demonstrated that LV20 combined with the adjuvant composed of DDA and Poly I: C (DP) elicited significantly higher antigen-specific antibodies and CD4(+)/CD8(+) T cell responses than PBS and BCG vaccination in mice. It suggests that the insect cell expression system is an excellent protein production system, and LV20 VLPs could be a novel tuberculosis vaccine candidate for further evaluation.
引用
收藏
页数:16
相关论文
共 66 条
  • [31] Kaufmann SHE, 2002, ANN RHEUM DIS, V61, P54
  • [32] Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries
    Knight, Gwenan M.
    Griffiths, Ulla K.
    Sumner, Tom
    Laurence, Yoko V.
    Gheorghe, Adrian
    Vassall, Anna
    Glaziou, Philippe
    White, Richard G.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (43) : 15520 - 15525
  • [33] Influenza virus-like particles as an antigen-carrier platform for the ESAT-6 epitope of Mycobacterium tuberculosis
    Krammer, Florian
    Schinko, Theresa
    Messner, Paul
    Palmberger, Dieter
    Ferko, Boris
    Grabherr, Reingard
    [J]. JOURNAL OF VIROLOGICAL METHODS, 2010, 167 (01) : 17 - 22
  • [34] Kinetics of dendritic cell activation:: impact on priming of TH1, TH2 and nonpolarized T cells
    Langenkamp, A
    Messi, M
    Lanzavecchia, A
    Sallusto, F
    [J]. NATURE IMMUNOLOGY, 2000, 1 (04) : 311 - 316
  • [35] A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice
    Liu, Xun
    Da, Zejiao
    Wang, Yue
    Niu, Hongxia
    Li, Ruiying
    Yu, Hongjuan
    He, Shanshan
    Guo, Ming
    Wang, Yong
    Luo, Yanping
    Ma, Xingming
    Zhu, Bingdong
    [J]. VACCINE, 2016, 34 (11) : 1370 - 1378
  • [36] Induction of a protective response with an IgA monoclonal antibody against Mycobacterium tuberculosis 16 kDa protein in a model of progressive pulmonary infection
    Lopez, Yamile
    Yero, Daniel
    Falero-Diaz, Gustavo
    Olivares, Nesty
    Sarmiento, Maria E.
    Sifontes, Sergio
    Solis, Rosa L.
    Barrios, Jorge A.
    Aguilar, Diana
    Hernandez-Pando, Rogelio
    Acosta, Armando
    [J]. INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 2009, 299 (06) : 447 - 452
  • [37] Lopez-Macias Constantino, 2012, Hum Vaccin Immunother, V8, P411, DOI 10.4161/hv.18757
  • [38] Bioengineering Virus-Like Particles as Vaccines
    Lua, Linda H. L.
    Connors, Natalie K.
    Sainsbury, Frank
    Chuan, Yap P.
    Wibowo, Nani
    Middelberg, Anton P. J.
    [J]. BIOTECHNOLOGY AND BIOENGINEERING, 2014, 111 (03) : 425 - 440
  • [39] First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
    Luabeya, Angelique Kany Kany
    Kagina, Benjamin M. N.
    Tameris, Michele D.
    Geldenhuys, Hennie
    Hoff, Soren T.
    Shi, Zhongkai
    Kromann, Ingrid
    Hatherill, Mark
    Mahomed, Hassan
    Hanekom, Willem A.
    Andersen, Peter
    Scriba, Thomas J.
    [J]. VACCINE, 2015, 33 (33) : 4130 - 4140
  • [40] Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials
    Mangtani, Punam
    Abubakar, Ibrahim
    Ariti, Cono
    Beynon, Rebecca
    Pimpin, Laura
    Fine, Paul E. M.
    Rodrigues, Laura C.
    Smith, Peter G.
    Lipman, Marc
    Whiting, Penny F.
    Sterne, Jonathan A.
    [J]. CLINICAL INFECTIOUS DISEASES, 2014, 58 (04) : 470 - 480