Loss of Lipid Virulence Factors Reduces the Efficacy of the BCG Vaccine.
Sci Rep
; 6: 29076, 2016 06 30.
Article
de En
| MEDLINE
| ID: mdl-27357109
ABSTRACT
Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. BCG comprises a number of substrains that exhibit genetic and biochemical differences. Whether and how these differences affect BCG efficacy remain unknown. Compared to other BCG strains, BCG-Japan, -Moreau, and -Glaxo are defective in the production of phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), two lipid virulence factors. To determine if the loss of PDIMs/PGLs affects BCG efficacy, we constructed a PDIM/PGL-deficient strain of BCG-Pasteur by deleting fadD28, and compared virulence, immunogenicity, and protective efficacy in animal models. SCID mouse infection experiments showed that ∆fadD28 was more attenuated than wild type (WT). The ∆fadD28 and WT strains induced equivalent levels of antigen specific IFN-γ by CD4(+) and CD8(+) T cells; however, ∆fadD28 was less effective against Mycobacterium tuberculosis challenge in both BALB/c mice and guinea pigs. These results indicate that the loss of PIDMs/PGLs reduces the virulence and protective efficacy of BCG. Since the loss of PDIMs/PGLs occurs naturally in a subset of BCG strains, it also suggests that these strains may have been over-attenuated, which compromises their effectiveness. Our finding has important implications for current BCG programs and future vaccine development.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tuberculose
/
Vaccin BCG
/
Glycolipides
/
Carbon-sulfur ligases
/
Lipides
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Pays/Région comme sujet:
Asia
Langue:
En
Journal:
Sci Rep
Année:
2016
Type de document:
Article
Pays d'affiliation:
Canada