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  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

Desel, C., Dorhoi, A., Bandermann, S., Grode, L., Eisele, B., & Kaufmann, S. H. E. (2011). 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. Journal of Infectious Diseases, 204(10), 1573-1584. doi:10.1093/infdis/jir592.

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Genre: Journal Article
Alternative Title : J. Infect. Dis.

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J_Inf_Dis_2011_204_1573.pdf (Publisher version), 508KB
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J_Inf_Dis_2011_204_1573.pdf
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© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
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 Creators:
Desel, Christiane1, Author              
Dorhoi, Anca1, Author              
Bandermann, Silke1, Author              
Grode, Leander2, Author
Eisele, Bernd, Author
Kaufmann, Stefan H. E.1, Author              
Affiliations:
1Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664146              
2External Organizations, ou_persistent22              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2011-11-15
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 574209
ISI: 000295990400015
DOI: 10.1093/infdis/jir592
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Title: Journal of Infectious Diseases
  Alternative Title : J. Infect. Dis.
Source Genre: Journal
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Publ. Info: CARY : OXFORD UNIV PRESS INC
Pages: - Volume / Issue: 204 (10) Sequence Number: - Start / End Page: 1573 - 1584 Identifier: ISSN: 0022-1899