Title :

Increased protective efficacy of recombinant BCG strains expressing virulence-neutral proteins of the ESX-1 secretion system

Author(s) :

Bottai, Daria [Auteur correspondant]
Pathogénomique mycobactérienne intégrée
Frigui, Wafa [Auteur]
Pathogénomique mycobactérienne intégrée
Clark, Simon [Auteur]
Public Health England [London]
Rayner, Emma [Auteur]
Public Health England [London]
Zelmer, Andrea [Auteur]
London School of Hygiene and Tropical Medicine [LSHTM]
Andreu, Nuria [Auteur]
London School of Hygiene and Tropical Medicine [LSHTM]
de Jonge, Marien I. [Auteur]
Bancroft, Gregory J. [Auteur]
London School of Hygiene and Tropical Medicine [LSHTM]
Williams, Ann [Auteur]
Public Health England [London]
Brodin, Priscille [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Brosch, Roland [Auteur correspondant]
Pathogénomique mycobactérienne intégrée

Journal title :

Vaccine

Pages :

2710-2718

Publisher :

Elsevier

Publication date :

2015-05-28

ISSN :

0264-410X

English keyword(s) :

ESAT-6 2
ESX-1 secretion system
recombinant BCG
Vaccine
Tuberculosis

HAL domain(s) :

Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]
Sciences du Vivant [q-bio]/Biologie cellulaire/Interactions cellulaires [q-bio.CB]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Nouveau vaccin BCG contre la tuberculose

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL