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  The Tuberculosis Vaccine Candidate Bacillus Calmette-Guérin ΔureC::hly Coexpressing Human Interleukin-7 or -18 Enhances Antigen-Specific T Cell Responses in Mice

Rao, M., Vogelzang, A., Kaiser, P., Schuerer, S., Kaufmann, S. H. E., & Gengenbacher, M. (2013). The Tuberculosis Vaccine Candidate Bacillus Calmette-Guérin ΔureC:hly Coexpressing Human Interleukin-7 or -18 Enhances Antigen-Specific T Cell Responses in Mice. PLoS One, 8(11): e78966. doi:10.1371/journal.pone.0078966.

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PLoS_One_2013_8_e78966.pdf (Publisher version), 711KB
 
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© 2013 Rao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 Creators:
Rao, Martin1, Author              
Vogelzang, Alexis1, Author              
Kaiser, Peggy1, Author              
Schuerer, Stefanie1, Author              
Kaufmann, Stefan H. E.1, Author              
Gengenbacher, Martin1, Author              
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1Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664146              

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 Abstract: Bacillus Calmette–Guérin (BCG), the only approved tuberculosis vaccine, provides only limited protection. Previously, we generated a recombinant derivative (BCG ΔureC::hly), which secretes the pore-forming toxin listeriolysin O (LLO) of Listeria monocytogenes. This vaccine shows superior protection against tuberculosis in preclinical models and is safe in humans. Here we describe two new vaccine strains which express human interleukin-7 (hIL)-7 or hIL-18 in the genetic background of BCG ΔureC::hly to modulate specific T cell immunity. Both strains exhibited an uncompromised in vitro growth pattern, while inducing a proinflammatory cytokine profile in human dendritic cells (DCs). Human DCs harbouring either strain efficiently promoted secretion of IL-2 by autologous T cells in a coculture system, suggesting superior immunogenicity. BALB/c mice vaccinated with BCG ΔureC::hly, BCG ΔureC::hly_hIL7 or BCG ΔureC::hly_hIL18 developed a more robust Th1 response than after vaccination with parental BCG. Both strains provided significantly better protection than BCG in a murine Mycobacterium tuberculosis challenge model but efficacy remained comparable to that afforded by BCG ΔureC::hly. We conclude that expression of hIL-7 or hIL-18 enhanced specific T cell responses but failed to improve protection over BCG ΔureC::hly in mice.

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Language(s): eng - English
 Dates: 2013-11-13
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pone.0078966
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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 8 (11) Sequence Number: e78966 Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850