In vivo targeting of human DC-SIGN drastically enhances CD8⁺ T-cell-mediated protective immunity.

2.50
Hdl Handle:
http://hdl.handle.net/10033/305604
Title:
In vivo targeting of human DC-SIGN drastically enhances CD8⁺ T-cell-mediated protective immunity.
Authors:
Hesse, Christina; Ginter, Wiebke; Förg, Theresa; Mayer, Christian T; Baru, Abdul Mannan; Arnold-Schrauf, Catharina; Unger, Wendy W J; Kalay, Hakan; van Kooyk, Yvette; Berod, Luciana; Sparwasser, Tim ( 0000-0001-5645-902X )
Abstract:
Vaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8⁺ T-cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC-SIGN (DC-specific-ICAM3-grabbing-nonintegrin/CD209) is a C-type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC-SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC-SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti-DC-SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti-DC-SIGN antibodies conjugated to OVA induced strong and persistent antigen-specific CD4⁺ and CD8⁺ T-cell responses, which efficiently protected from infection with OVA-expressing Listeria monocytogenes. Thus, we propose DC targeting via DC-SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens.
Affiliation:
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Citation:
In vivo targeting of human DC-SIGN drastically enhances CD8⁺ T-cell-mediated protective immunity. 2013, 43 (10):2543-53 Eur. J. Immunol.
Journal:
European journal of immunology
Issue Date:
Oct-2013
URI:
http://hdl.handle.net/10033/305604
DOI:
10.1002/eji.201343429
PubMed ID:
23784881
Type:
Article
Language:
en
ISSN:
1521-4141
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorHesse, Christinaen
dc.contributor.authorGinter, Wiebkeen
dc.contributor.authorFörg, Theresaen
dc.contributor.authorMayer, Christian Ten
dc.contributor.authorBaru, Abdul Mannanen
dc.contributor.authorArnold-Schrauf, Catharinaen
dc.contributor.authorUnger, Wendy W Jen
dc.contributor.authorKalay, Hakanen
dc.contributor.authorvan Kooyk, Yvetteen
dc.contributor.authorBerod, Lucianaen
dc.contributor.authorSparwasser, Timen
dc.date.accessioned2013-11-21T09:48:03Zen
dc.date.available2013-11-21T09:48:03Zen
dc.date.issued2013-10en
dc.identifier.citationIn vivo targeting of human DC-SIGN drastically enhances CD8⁺ T-cell-mediated protective immunity. 2013, 43 (10):2543-53 Eur. J. Immunol.en
dc.identifier.issn1521-4141en
dc.identifier.pmid23784881en
dc.identifier.doi10.1002/eji.201343429en
dc.identifier.urihttp://hdl.handle.net/10033/305604en
dc.description.abstractVaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8⁺ T-cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC-SIGN (DC-specific-ICAM3-grabbing-nonintegrin/CD209) is a C-type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC-SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC-SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti-DC-SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti-DC-SIGN antibodies conjugated to OVA induced strong and persistent antigen-specific CD4⁺ and CD8⁺ T-cell responses, which efficiently protected from infection with OVA-expressing Listeria monocytogenes. Thus, we propose DC targeting via DC-SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens.en
dc.language.isoenen
dc.rightsArchived with thanks to European journal of immunologyen
dc.titleIn vivo targeting of human DC-SIGN drastically enhances CD8⁺ T-cell-mediated protective immunity.en
dc.typeArticleen
dc.contributor.departmentInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.en
dc.identifier.journalEuropean journal of immunologyen

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