TY - JOUR
T1 - Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent Infection
AU - Li, F.
AU - Kang, H.
AU - Li, J.
AU - Zhang, D.
AU - Zhang, Y.
AU - Dannenberg, A. M.
AU - Liu, X.
AU - Niu, H.
AU - Ma, L.
AU - Tang, R.
AU - Han, X.
AU - Gan, C.
AU - Ma, X.
AU - Tan, J.
AU - Zhu, B.
N1 - Publisher Copyright:
© 2017 The Foundation for the Scandinavian Journal of Immunology
PY - 2017/6
Y1 - 2017/6
N2 - 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), ESAT6-Rv1738-Rv2626c (LT40), ESAT6-Ag85B-MPT64<190-198>-Mtb8.4 (EAMM), and EAMM-Rv2626c (LT70) 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 LT40 and LT70 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.
AB - 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), ESAT6-Rv1738-Rv2626c (LT40), ESAT6-Ag85B-MPT64<190-198>-Mtb8.4 (EAMM), and EAMM-Rv2626c (LT70) 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 LT40 and LT70 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.
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U2 - 10.1111/sji.12556
DO - 10.1111/sji.12556
M3 - Article
C2 - 28426145
AN - SCOPUS:85019679709
SN - 0300-9475
VL - 85
SP - 425
EP - 432
JO - Scandinavian Journal of Immunology
JF - Scandinavian Journal of Immunology
IS - 6
ER -