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          Institute: MPI für Infektionsbiologie     Collection: Department of Immunology     Display Documents



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ID: 574209.0, MPI für Infektionsbiologie / Department of Immunology
Recombinant BCG Delta ureC hly plus Induces Superior Protection Over Parental BCG by Stimulating a Balanced Combination of Type 1 and Type 17 Cytokine Responses
Authors:Desel, Christiane; Dorhoi, Anca; Bandermann, Silke; Grode, Leander; Eisele, Bernd; Kaufmann, Stefan H. E.
Language:English
Date of Publication (YYYY-MM-DD):2011-11-15
Title of Journal:Journal of Infectious Diseases
Journal Abbrev.:J. Infect. Dis.
Volume:204
Issue / Number:10
Start Page:1573
End Page:1584
Copyright:© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Background. New vaccines against tuberculosis (TB) are urgently needed because the only available vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), fails to protect against pulmonary TB in adults. The recombinant Delta ureC 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.
Comment of the Author/Creator:Acknowledgments:  We thank M. L. Grossman for help in preparing the manuscript and C. Köberle for the FACS data analyzer software.
Financial support: This work was supported by the European Commission's Framework Programme 6 TBVAC (LSHP-CT-2003-503367 to S. H. E. K.); and the European Commission's Framework Programme 7 NEWTBVAC (Health-F3-2009-241745 to S. H. E. K.).
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Immunology
External Affiliations:[Grode, L; Eisele, B] Vakzine Projekt Management, Hannover, Germany.
Identifiers:ISI:000295990400015 [ID No:1]
ISSN:0022-1899 [ID No:2]
DOI:10.1093/infdis/jir592 [ID No:3]
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