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Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis.
- Source :
-
Molecular immunology [Mol Immunol] 2015 Aug; Vol. 66 (2), pp. 392-401. Date of Electronic Publication: 2015 May 18. - Publication Year :
- 2015
-
Abstract
- Although Bacillus Calmette-Guérin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. Here, a novel cocktail of recombinant BCG (rBCG) strains, namely ABX, was produced by combining rBCG::85A, rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A, Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of IFN-γ(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antibodies, Bacterial biosynthesis
Antibodies, Bacterial blood
Antigen Presentation drug effects
Apoptosis drug effects
Female
Gene Expression
Immunity, Cellular drug effects
Immunity, Humoral drug effects
Immunodominant Epitopes genetics
Interferon-gamma biosynthesis
Interferon-gamma immunology
Interleukin-2 biosynthesis
Interleukin-2 immunology
Macrophages drug effects
Macrophages immunology
Macrophages microbiology
Mice
Mice, Inbred C57BL
Mycobacterium bovis chemistry
Mycobacterium bovis immunology
Recombinant Fusion Proteins administration & dosage
Recombinant Fusion Proteins genetics
Th1 Cells immunology
Tuberculosis genetics
Tuberculosis immunology
Tuberculosis Vaccines administration & dosage
Tuberculosis Vaccines genetics
Vaccination
Immunodominant Epitopes immunology
Mycobacterium bovis genetics
Mycobacterium tuberculosis immunology
Recombinant Fusion Proteins immunology
Th1 Cells drug effects
Tuberculosis prevention & control
Tuberculosis Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 66
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 25974877
- Full Text :
- https://doi.org/10.1016/j.molimm.2015.04.017