Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis
Open accessAbstract
The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (RD1) locus, which is intact in virulent members of the Mycobacterium tuberculosis complex. To increase their immunogenicity and protective capacity, we complemented both vaccines with different constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, as well as a variable number of flanking genes. Only reintroduction of the complete locus, comprising at least 11 genes, led to full secretion of the antigens and resulted in specific ESAT-6-dependent immune responses; this suggests that the flanking genes encode a secretory apparatus. Mice and guinea pigs vaccinated with the recombinant strain BCG::RD1-2F9 were better protected against challenge with M. tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone.
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Several recombinant BCG vaccine candidates have been constructed to overcome these limitations of BCG.
“Several recombinant BCG vaccine candidates have been constructed to overcome these limitations of BCG (75,(87)(88)(89)(90).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [87]
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Self-citation
- Authors
- Pym, A. S., Brodin, P., Majlessi, L., Brosch, R., Demangel, C., Williams, A., Griffiths, K. E., Marchal, G., Leclerc, C., & Cole, S. T.
- Affiliations
- Institut Pasteur (FR)
- Inserm (FR)
- Corresponding author
- Cole, Stewart T.
- ORCID
- Venue
- Nature Medicine
- Published
- 2003-04-14
- Volume
- 9
- Issue
- 5
- Pages
- 533-539
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1985004048
- Cited by
- 644
- References
- 44
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 18 · 2023: 14 · 2022: 8 · 2021: 19 · 2020: 20 · 2019: 19 · 2018: 19 · 2017: 22 · 2016: 32 · 2015: 29 · 2014: 20 · 2013: 32 · 2012: 35
- FWCI
- 28.16
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- ESAT-6, CFP-10, Mycobacterium bovis BCG, Mycobacterium microti, tuberculosis vaccine, antigen secretion, recombinant BCG, Mycobacterium tuberculosis, vaccine protection, T cell response, secretory apparatus, gene complementation
- MeSH terms
- Animals, Antigens, Bacterial, Bacterial Proteins, BCG Vaccine, Chromosome Mapping, Female, Guinea Pigs, Mice, Inbred C57BL, Mycobacterium tuberculosis, T-Lymphocytes, Tuberculosis, Vaccination, Vaccines, Synthetic, Gene Deletion, Protein Transport, Mice
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