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Increased protective efficacy of recombinant BCG strains expressing virulence-neutral proteins of the ESX-1 secretion system
- Source :
- Vaccine, Vaccine, 2015, 33 (23), pp.2710-2718. ⟨10.1016/j.vaccine.2015.03.083⟩, Vaccine, 33, 2710-2718, Vaccine, 33, 23, pp. 2710-2718, Vaccine, Elsevier, 2015, 33 (23), pp.2710-2718. ⟨10.1016/j.vaccine.2015.03.083⟩
- Publication Year :
- 2015
-
Abstract
- Background Mycobacterium bovis BCG is presently the only available anti-tuberculosis vaccine used, worldwide. While BCG protects against miliary tuberculosis (TB) and tuberculoid meningitis in children, it often fails to protect against adult pulmonary TB. It is thus imperative that new improved anti-TB vaccines are developed. The integration of the ESX-1 secretion system, absent from BCG due to the deletion of region of difference 1 (RD1), into the genome of BCG has been shown to confer to BCG::ESX-1 enhanced protection against TB as compared to BCG. Methods In the present study, to counterbalance the increase in virulence resulting from the integration of the RD1 region into BCG, we have constructed and evaluated several BCG::ESX-1 variants that carry selected amino-acid changes in the ESX-1-secreted antigen ESAT-6. In order to find the candidate that combines low virulence with high protective efficacy, these novel recombinant BCG::ESX-1 strains were tested for their virulence properties and their protective efficacy against Mycobacterium tuberculosis in two different animal models (mouse and guinea-pig). Results Among several candidates tested, the BCG::ESAT-L28A/L29S strain, carrying modifications at residues Leu 28 -Leu 29 of the ESAT molecule, showed strong attenuation in mice and high protective efficiency both in mouse and guinea-pig vaccination-infection models. Conclusion This strain thus represents a promising candidate that merits further investigations and development. Our research also provides the proof of concept that selected ESX-1-complemented BCG strains may show low virulence and increased protective potential over parental strains.
- Subjects :
- Male
ESX-1 secretion system
ESAT-6 2
Immunology and Microbiology (all)
[SDV]Life Sciences [q-bio]
Colony Count
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
recombinant BCG
Colony Count, Microbial
Mice, SCID
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Inbred C57BL
Mice
Microbial
ESAT-6
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Lung
Mycobacterium bovis
Vaccines
Vaccines, Synthetic
Virulence
Medicine (all)
Bacterial
3. Good health
[SDV] Life Sciences [q-bio]
Infectious Diseases
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Treatment Outcome
BCG Vaccine
Veterinary (all)
Molecular Medicine
Female
Public Health
Tuberculosis
Guinea Pigs
Biology
SCID
complex mixtures
Microbiology
Mycobacterium tuberculosis
Antigen
Bacterial Proteins
medicine
Animals
Secretion
Antigens
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Antigens, Bacterial
General Veterinary
General Immunology and Microbiology
Synthetic
Environmental and Occupational Health
Public Health, Environmental and Occupational Health
biology.organism_classification
medicine.disease
Virology
Survival Analysis
Mice, Inbred C57BL
Recombinant BCG
Vaccine
Spleen
BCG vaccine
Subjects
Details
- ISSN :
- 18732518, 0264410X, and 27102718
- Volume :
- 33
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....248d141db153eb2bd81dcfcb1b976aeb