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J Infect Dis. 2014 Dec 15;210(12):1928-37. doi: 10.1093/infdis/jiu347. Epub 2014 Jun 18.

Central memory CD4+ T cells are responsible for the recombinant Bacillus Calmette-Guérin ΔureC::hly vaccine's superior protection against tuberculosis.

Author information

1
Department of Immunology.
2
Core Facility Protein Purification, Max Planck Institute for Infection Biology, Berlin, Germany.

Abstract

Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis for nearly a century. Here, we analyze immunity induced by a live tuberculosis vaccine candidate, recombinant BCG ΔureC::hly vaccine (rBCG), with proven preclinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4(+) T-cell population, comparing the more efficacious rBCG with canonical BCG to determine which T-cell memory responses are prerequisites for superior protection against tuberculosis. rBCG induced higher numbers and proportions of antigen-specific memory CD4(+) T cells than BCG, with a CXCR5(+)CCR7(+) phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We found that the superior protection of rBCG, compared with BCG, correlated with higher proportions and numbers of these central memory T cells and of T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary tuberculosis.

KEYWORDS:

BCG; Mycobacterium tuberculosis; VPM1002; memory T cells; vaccine; ΔureC::hly

PMID:
24943726
PMCID:
PMC4241943
DOI:
10.1093/infdis/jiu347
[Indexed for MEDLINE]
Free PMC Article

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