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J Infect Dis. 2011 Nov 15;204(10):1573-84. doi: 10.1093/infdis/jir592. Epub 2011 Sep 20.

Recombinant BCG ΔureC hly+ induces superior protection over parental BCG by stimulating a balanced combination of type 1 and type 17 cytokine responses.

Author information

1
Department of Immunology, Max Planck Institute for Infection Biology, Berlin. kaufmann@mpiib-berlin.mpg.de

Abstract

BACKGROUND:

New vaccines against tuberculosis (TB) are urgently needed because the only available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to protect against pulmonary TB in adults. The recombinant ΔureC hly+ BCG (rBCG) is more efficient than parental BCG (pBCG) against pulmonary TB in preclinical studies and has proven safe and immunogenic in phase I clinical trials.

METHODS:

In an attempt to identify the mechanisms underlying the superior protection of rBCG, we compared the immune responses elicited after vaccination and subsequent aerosol infection with Mycobacterium tuberculosis (MTB) in mice.

RESULTS:

We demonstrate that both rBCG and pBCG induce marked type 1 cytokine responses, whereas only rBCG elicits a profound type 17 cytokine response in addition. We observed earlier recruitment of antigen-specific T lymphocytes to the lung upon MTB infection of rBCG-vaccinated mice. These T cells produced abundant type 1 cytokines after restimulation, resulting in 10-fold reduced bacterial burden 90 days after infection.

CONCLUSIONS:

Our findings identify a general immunologic pathway for improved vaccination strategies against TB that can also be harnessed by other vaccine candidates.

PMID:
21933877
PMCID:
PMC3192191
DOI:
10.1093/infdis/jir592
[Indexed for MEDLINE]
Free PMC Article
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