Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses

Autores
Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; Lycke, Nils Yngve; Barkan, Daniel; Martina, Mariana Andrea; Lujan, Hugo Daniel; Kalay, Hakan; van Kooyk, Yvette; Sparwasser, Tim D.; Berod, Luciana
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections.
Fil: Velasquez, Lis Noelia. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; Alemania
Fil: Stüve, Philipp. Medical School Hannover; Alemania. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Gentilini, Maria Virginia. Medical School Hannover; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Swallow, Maxine. Medical School Hannover; Alemania. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Bartel, Judith. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; Alemania
Fil: Lycke, Nils Yngve. Universidad de Gotemburgo; Suecia
Fil: Barkan, Daniel. The Hebrew University of Jerusalem; Israel
Fil: Martina, Mariana Andrea. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lujan, Hugo Daniel. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kalay, Hakan. VU University Medical Center; Países Bajos
Fil: van Kooyk, Yvette. VU University Medical Center; Países Bajos
Fil: Sparwasser, Tim D.. Centre for Experimental and Clinical Infection Research; Alemania. Medical School Hannover; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Berod, Luciana. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; Alemania
Materia
AG85B
DC-SPECIFIC-ICAM3-GRABBING-NONINTEGRIN
DENDRITIC CELLS
TUBERCULOSIS
VACCINE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/99508
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/99508
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responsesVelasquez, Lis NoeliaStüve, PhilippGentilini, Maria VirginiaSwallow, MaxineBartel, JudithLycke, Nils YngveBarkan, DanielMartina, Mariana AndreaLujan, Hugo DanielKalay, Hakanvan Kooyk, YvetteSparwasser, Tim D.Berod, LucianaAG85BDC-SPECIFIC-ICAM3-GRABBING-NONINTEGRINDENDRITIC CELLSTUBERCULOSISVACCINEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections.Fil: Velasquez, Lis Noelia. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; AlemaniaFil: Stüve, Philipp. Medical School Hannover; Alemania. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Gentilini, Maria Virginia. Medical School Hannover; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Swallow, Maxine. Medical School Hannover; Alemania. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Bartel, Judith. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; AlemaniaFil: Lycke, Nils Yngve. Universidad de Gotemburgo; SueciaFil: Barkan, Daniel. The Hebrew University of Jerusalem; IsraelFil: Martina, Mariana Andrea. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lujan, Hugo Daniel. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kalay, Hakan. VU University Medical Center; Países BajosFil: van Kooyk, Yvette. VU University Medical Center; Países BajosFil: Sparwasser, Tim D.. Centre for Experimental and Clinical Infection Research; Alemania. Medical School Hannover; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Berod, Luciana. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; AlemaniaFrontiers Media S.A.2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99508Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; et al.; Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; MAR; 3-2018; 1-141664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2018.00471/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.00471info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:44:30Zoai:ri.conicet.gov.ar:11336/99508instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:44:31.177CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
title Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
spellingShingle Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
Velasquez, Lis Noelia
AG85B
DC-SPECIFIC-ICAM3-GRABBING-NONINTEGRIN
DENDRITIC CELLS
TUBERCULOSIS
VACCINE
title_short Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
title_full Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
title_fullStr Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
title_full_unstemmed Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
title_sort Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
dc.creator.none.fl_str_mv Velasquez, Lis Noelia
Stüve, Philipp
Gentilini, Maria Virginia
Swallow, Maxine
Bartel, Judith
Lycke, Nils Yngve
Barkan, Daniel
Martina, Mariana Andrea
Lujan, Hugo Daniel
Kalay, Hakan
van Kooyk, Yvette
Sparwasser, Tim D.
Berod, Luciana
author Velasquez, Lis Noelia
author_facet Velasquez, Lis Noelia
Stüve, Philipp
Gentilini, Maria Virginia
Swallow, Maxine
Bartel, Judith
Lycke, Nils Yngve
Barkan, Daniel
Martina, Mariana Andrea
Lujan, Hugo Daniel
Kalay, Hakan
van Kooyk, Yvette
Sparwasser, Tim D.
Berod, Luciana
author_role author
author2 Stüve, Philipp
Gentilini, Maria Virginia
Swallow, Maxine
Bartel, Judith
Lycke, Nils Yngve
Barkan, Daniel
Martina, Mariana Andrea
Lujan, Hugo Daniel
Kalay, Hakan
van Kooyk, Yvette
Sparwasser, Tim D.
Berod, Luciana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AG85B
DC-SPECIFIC-ICAM3-GRABBING-NONINTEGRIN
DENDRITIC CELLS
TUBERCULOSIS
VACCINE
topic AG85B
DC-SPECIFIC-ICAM3-GRABBING-NONINTEGRIN
DENDRITIC CELLS
TUBERCULOSIS
VACCINE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections.
Fil: Velasquez, Lis Noelia. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; Alemania
Fil: Stüve, Philipp. Medical School Hannover; Alemania. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Gentilini, Maria Virginia. Medical School Hannover; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Swallow, Maxine. Medical School Hannover; Alemania. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Bartel, Judith. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; Alemania
Fil: Lycke, Nils Yngve. Universidad de Gotemburgo; Suecia
Fil: Barkan, Daniel. The Hebrew University of Jerusalem; Israel
Fil: Martina, Mariana Andrea. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lujan, Hugo Daniel. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kalay, Hakan. VU University Medical Center; Países Bajos
Fil: van Kooyk, Yvette. VU University Medical Center; Países Bajos
Fil: Sparwasser, Tim D.. Centre for Experimental and Clinical Infection Research; Alemania. Medical School Hannover; Alemania. Helmholtz Centre for Infection Research; Alemania
Fil: Berod, Luciana. Centre for Experimental and Clinical Infection Research; Alemania. Helmholtz Centre for Infection Research; Alemania. Medical School Hannover; Alemania
description Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/99508
Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; et al.; Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; MAR; 3-2018; 1-14
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99508
identifier_str_mv Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; et al.; Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; MAR; 3-2018; 1-14
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2018.00471/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.00471
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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