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PLoS One. 2011;6(5):e19840. doi: 10.1371/journal.pone.0019840. Epub 2011 May 24.

Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy.

Author information

1
The Jenner Institute, University of Oxford, Oxford, United Kingdom. minassian.angela@gmail.com

Abstract

There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection.

PMID:
21629699
PMCID:
PMC3101220
DOI:
10.1371/journal.pone.0019840
[Indexed for MEDLINE]
Free PMC Article

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