NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin
Bacterial flagellin enhances innate and adaptive immune responses and is considered a promising adjuvant for the development of vaccines against infectious diseases and cancer. Antigen-presenting cells recognize flagellin with the extracellular TLR5 and the intracellular NLRC4 inflammasome-mediated...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01988/full |
| _version_ | 1818193239467884544 |
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| author | Stephanie L. Sanos Ronny Kassub Marco Testori Marlene Geiger Juliane Pätzold Raphael Giessel Johanna Knallinger Barbara Bathke Fabienne Gräbnitz Kay Brinkmann Paul Chaplin Mark Suter Hubertus Hochrein Henning Lauterbach |
| author_facet | Stephanie L. Sanos Ronny Kassub Marco Testori Marlene Geiger Juliane Pätzold Raphael Giessel Johanna Knallinger Barbara Bathke Fabienne Gräbnitz Kay Brinkmann Paul Chaplin Mark Suter Hubertus Hochrein Henning Lauterbach |
| author_sort | Stephanie L. Sanos |
| collection | DOAJ |
| description | Bacterial flagellin enhances innate and adaptive immune responses and is considered a promising adjuvant for the development of vaccines against infectious diseases and cancer. Antigen-presenting cells recognize flagellin with the extracellular TLR5 and the intracellular NLRC4 inflammasome-mediated pathway. The detailed cooperation of these innate pathways in the induction of the adaptive immune response following intranasal (i.n.) administration of a recombinant modified vaccinia virus Ankara (rMVA) vaccine encoding flagellin (rMVA-flagellin) is not known. rMVA-flagellin induced enhanced secretion of mucosal IL-1β and TNF-α resulting in elevated CTL and IgG2c antibody responses. Importantly, mucosal IgA responses were also significantly enhanced in both bronchoalveolar (BAL) and intestinal lavages accompanied by the increased migration of CD8+ T cells to the mesenteric lymph nodes (MLN). Nlrc4−/− rMVA-flagellin-immunized mice failed to enhance pulmonary CTL responses, IgG2c was lower, and IgA levels in the BAL or intestinal lavages were similar as those of control mice. Our results show the favorable adjuvant effect of rMVA-flagellin in the lung as well as the intestinal mucosa following i.n. administration with NLRC4 as the essential driver of this promising mucosal vaccine concept. |
| first_indexed | 2024-12-12T00:43:14Z |
| format | Article |
| id | doaj.art-202827b76b0b4fcf92533824f7ea76ce |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T00:43:14Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-202827b76b0b4fcf92533824f7ea76ce2022-12-22T00:44:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.01988294317NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding FlagellinStephanie L. Sanos0Ronny Kassub1Marco Testori2Marlene Geiger3Juliane Pätzold4Raphael Giessel5Johanna Knallinger6Barbara Bathke7Fabienne Gräbnitz8Kay Brinkmann9Paul Chaplin10Mark Suter11Hubertus Hochrein12Henning Lauterbach13Bavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyUniversity of Zurich, Zurich, SwitzerlandBavarian Nordic GmbH, Martinsried, GermanyBavarian Nordic GmbH, Martinsried, GermanyBacterial flagellin enhances innate and adaptive immune responses and is considered a promising adjuvant for the development of vaccines against infectious diseases and cancer. Antigen-presenting cells recognize flagellin with the extracellular TLR5 and the intracellular NLRC4 inflammasome-mediated pathway. The detailed cooperation of these innate pathways in the induction of the adaptive immune response following intranasal (i.n.) administration of a recombinant modified vaccinia virus Ankara (rMVA) vaccine encoding flagellin (rMVA-flagellin) is not known. rMVA-flagellin induced enhanced secretion of mucosal IL-1β and TNF-α resulting in elevated CTL and IgG2c antibody responses. Importantly, mucosal IgA responses were also significantly enhanced in both bronchoalveolar (BAL) and intestinal lavages accompanied by the increased migration of CD8+ T cells to the mesenteric lymph nodes (MLN). Nlrc4−/− rMVA-flagellin-immunized mice failed to enhance pulmonary CTL responses, IgG2c was lower, and IgA levels in the BAL or intestinal lavages were similar as those of control mice. Our results show the favorable adjuvant effect of rMVA-flagellin in the lung as well as the intestinal mucosa following i.n. administration with NLRC4 as the essential driver of this promising mucosal vaccine concept.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01988/fullmucosal vaccinesMVAflagellininflammasomeintestinal mucosa |
| spellingShingle | Stephanie L. Sanos Ronny Kassub Marco Testori Marlene Geiger Juliane Pätzold Raphael Giessel Johanna Knallinger Barbara Bathke Fabienne Gräbnitz Kay Brinkmann Paul Chaplin Mark Suter Hubertus Hochrein Henning Lauterbach NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin Frontiers in Immunology mucosal vaccines MVA flagellin inflammasome intestinal mucosa |
| title | NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin |
| title_full | NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin |
| title_fullStr | NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin |
| title_full_unstemmed | NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin |
| title_short | NLRC4 Inflammasome-Driven Immunogenicity of a Recombinant MVA Mucosal Vaccine Encoding Flagellin |
| title_sort | nlrc4 inflammasome driven immunogenicity of a recombinant mva mucosal vaccine encoding flagellin |
| topic | mucosal vaccines MVA flagellin inflammasome intestinal mucosa |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01988/full |
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