A human challenge model for Mycobacterium tuberculosis using Mycobacterium bovis bacille Calmette-Guerin.
J Infect Dis
; 205(7): 1035-42, 2012 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-22396610
ABSTRACT
BACKGROUND:
There is currently no safe human challenge model of Mycobacterium tuberculosis infection to enable proof-of-concept efficacy evaluation of candidate vaccines against tuberculosis. In vivo antimycobacterial immunity could be assessed using intradermal Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination as a surrogate for M. tuberculosis infection.METHODS:
Healthy BCG-naive and BCG-vaccinated volunteers were challenged with intradermal BCG. BCG load was quantified from skin biopsy specimens by polymerase chain reaction (PCR) and culture colony-forming units. Cellular infiltrate was isolated by suction blisters and examined by flow cytometry. Prechallenge immune readouts were correlated with BCG load after challenge.RESULTS:
In BCG-naive volunteers, live BCG was detected at the challenge site for up to 4 weeks and peaked at 2 weeks. Infiltration of mainly CD15(+) neutrophils was observed in blister fluid. In previously BCG-vaccinated individuals, PCR analysis of skin biopsy specimens reflected a degree of mycobacterial immunity. There was no significant correlation between BCG load after challenge and mycobacterial-specific memory T cells measured before challenge by cultured enzyme-linked immunospot assay.CONCLUSIONS:
This novel experimental human challenge model provides a platform for the identification of correlates of antimycobacterial immunity and will greatly facilitate the rational down-selection of candidate tuberculosis vaccines. Further evaluation of this model with BCG and new vaccine candidates is warranted.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Mycobacterium bovis
Limite:
Humans
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido