Recombinant BCG ΔureC hly+ Induces Superior Protection Over Parental BCG by Stimulating a Balanced Combination of Type 1 and Type 17 Cytokine Responses
Open Access
- 20 September 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 204 (10), 1573-1584
- https://doi.org/10.1093/infdis/jir592
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.Keywords
This publication has 44 references indexed in Scilit:
- Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosisThe Journal of Experimental Medicine, 2010
- Investigating the Induction of Vaccine-Induced Th17 and Regulatory T Cells in Healthy,Mycobacterium bovisBCG-Immunized Adults Vaccinated with a New Tuberculosis Vaccine, MVA85AClinical and Vaccine Immunology, 2010
- The Novel Tuberculosis Vaccine, AERAS-402, Induces Robust and Polyfunctional CD4+and CD8+T Cells in AdultsAmerican Journal of Respiratory and Critical Care Medicine, 2010
- Modified vaccinia Ankara‐expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cellsEuropean Journal of Immunology, 2009
- A Mutation in the Nlrp3 Gene Causing Inflammasome Hyperactivation Potentiates Th17 Cell-Dominant Immune ResponsesImmunity, 2009
- Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant Δ ureC hly + Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine TuberculosisInfection and Immunity, 2009
- γδ T cells: an important source of IL-17Current Opinion in Immunology, 2008
- Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania majorNature Medicine, 2007
- Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptidesThe Journal of Experimental Medicine, 2006
- Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cellsNature, 2006