Targeting Antigens to Dendritic Cells the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses.
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Authors
Velasquez, Lis NoeliaStüve, Philipp
Gentilini, Maria Virginia
Swallow, Maxine
Bartel, Judith
Lycke, Nils Yngve
Barkan, Daniel
Martina, Mariana
Lujan, Hugo D
Kalay, Hakan
van Kooyk, Yvette
Sparwasser, Tim D
Berod, Luciana
Issue Date
2018-01-01
Metadata
Show full item recordAbstract
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-specifc-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-specifc CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specifc 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 effciently exploited for vaccine purposes to promote immunity against mycobacterial infections.Affiliation
TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.PubMed ID
29662482Type
ArticleISSN
1664-3224ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2018.00471
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- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
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