title: Hepatitis B virus core particles displaying Mycobacterium tuberculosis antigen ESAT-6 enhance ESAT-6-specific immune responses.
abstract: Early secreted antigenic target-6 (ESAT-6), an important Mycobacterium tuberculosis T-cell antigen, is an attractive candidate antigen for tuberculosis subunit vaccine development. Because ESAT-6 has a low inherent immunogenicity, we used Hepatitis B virus core (HBc) protein as an immune carrier to enhance ESAT-6 immunogenicity. The ESAT-6 gene was inserted into the major immunodominant region of the HBc molecule by fusion PCR. The recombinant protein, HBc-ESAT-6 (HE6), was expressed in Escherichia coli, and electron microscopy confirmed the formation of virus-like particles. The immunogenicity of the chimeric particles was assessed in mice. Serological assays and in vitro Th1-biased cytokine assays found that immunization with HE6 particles elicited significantly higher ESAT-6-specific antibodies and CD4⁺/CD8⁺ T cell responses in mice compared to immunization with recombinant ESAT-6 protein. These data demonstrate the feasibility of HBc particles serving as an efficient immune carrier for ESAT-6 and suggest that HE6 has potential for use in a tuberculosis subunit vaccine.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongdajie, Fengtai, Beijing 100071, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Shipo
authors.initials: S
authors.lastname: Wu
authors.forename: Dayong
authors.initials: D
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma