hly coexpressing human interleukin-7 or -18 enhances antigen-specific T cell responses in mice
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
PloS one - 8(2013), 11 vom: 21., Seite e78966 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rao, Martin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
147205-72-9 |
|---|
| Anmerkungen: |
Date Completed 02.09.2014 Date Revised 21.10.2021 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0078966 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM232688338 |
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| 100 | 1 | |a Rao, Martin |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The tuberculosis vaccine candidate Bacillus Calmette-Guérin ΔureC::hly coexpressing human interleukin-7 or -18 enhances antigen-specific T cell responses in mice |
| 264 | 1 | |c 2013 | |
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| 500 | |a Date Completed 02.09.2014 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antigens, Bacterial |2 NLM | |
| 650 | 7 | |a BCG Vaccine |2 NLM | |
| 650 | 7 | |a IL18 protein, human |2 NLM | |
| 650 | 7 | |a IL7 protein, human |2 NLM | |
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| 700 | 1 | |a Schuerer, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Kaufmann, Stefan H E |e verfasserin |4 aut | |
| 700 | 1 | |a Gengenbacher, Martin |e verfasserin |4 aut | |
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