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Targeting Antigens to Dendritic Cells the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses.
Velasquez, Lis Noelia Stüve, Philipp Gentilini, Maria Virginia Swallow, Maxine Bartel, Judith Lycke, Nils Yngve Barkan, Daniel Martina, Mariana Lujan, Hugo D Kalay, Hakan
Velasquez, Lis Noelia
Stüve, Philipp
Gentilini, Maria Virginia
Swallow, Maxine
Bartel, Judith
Lycke, Nils Yngve
Barkan, Daniel
Martina, Mariana
Lujan, Hugo D
Kalay, Hakan
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2018-01-01
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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.
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1664-3224
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Attribution-NonCommercial-ShareAlike 3.0 United States