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Journal Article

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

MPS-Authors
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Rao,  Martin
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Vogelzang,  Alexis
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Kaiser,  Peggy
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Schuerer,  Stefanie
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Kaufmann,  Stefan H. E.
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Gengenbacher,  Martin
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Citation

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.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0015-3F6A-A
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.