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Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent Infection
Author(s) -
Li F.,
Kang H.,
Li J.,
Zhang D.,
Zhang Y.,
Dannenberg A. M.,
Liu X.,
Niu H.,
Ma L.,
Tang R.,
Han X.,
Gan C.,
Ma X.,
Tan J.,
Zhu B.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12556
Subject(s) - immunogenicity , mycobacterium bovis , antigen , biology , microbiology and biotechnology , mycobacterium tuberculosis , protein subunit , mycobacterium , virology , bacteria , immunology , tuberculosis , medicine , biochemistry , genetics , pathology , gene
To screen effective antigens as therapeutic subunit vaccines against Mycobacterium latent infection, we did bioinformatics analysis and literature review to identify effective antigens and evaluated the immunogenicity of five antigens highly expressed in dormant bacteria, which included Rv2031c (HspX), Rv2626c (Hrp1), Rv2007c (FdxA), Rv1738 and Rv3130c. Then, several fusion proteins such as Rv2007c‐Rv2626c (F6), Rv2031c‐Rv1738‐Rv1733c (H83), ESAT 6‐Rv1738‐Rv2626c ( LT 40), ESAT 6‐Ag85B‐ MPT 64 <190‐198> ‐Mtb8.4 ( EAMM ), and EAMM ‐Rv2626c ( LT 70) were constructed and their therapeutic effects were evaluated in pulmonary Mycobacterium bovis Bacilli Calmette–Guérin ( BCG ) – latently infected rabbit or mouse models. The results showed that EAMM and F6 plus H83 had therapeutic effect against BCG latent infection in the rabbit model, respectively, and that the combination of EAMM with F6 plus H83 significantly reduced the bacterial load. In addition, the fusion proteins LT 40 and LT 70 consisting of multistage antigens showed promising therapeutic effects in the mouse model. We conclude that subunit vaccines consisting of both latency and replicating‐associated antigens show promising therapeutic effects in BCG latent infection animal models.