%A Velasquez,Lis Noelia %A Stüve,Philipp %A Gentilini,Maria Virginia %A Swallow,Maxine %A Bartel,Judith %A Lycke,Nils Yngve %A Barkan,Daniel %A Martina,Mariana %A Lujan,Hugo D. %A Kalay,Hakan %A van Kooyk,Yvette %A Sparwasser,Tim D. %A Berod,Luciana %D 2018 %J Frontiers in Immunology %C %F %G English %K DC-SIGN,Tuberculosis,Vaccine,Dendritic Cells,Ag85B %Q %R 10.3389/fimmu.2018.00471 %W %L %M %P %7 %8 2018-March-09 %9 Original Research %+ Dr Luciana Berod,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),Germany,luciana.berod@twincore.de %# %! Tuberculosis vaccine via DC-SIGN targeting %* %< %T Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses %U https://www.frontiersin.org/articles/10.3389/fimmu.2018.00471 %V 9 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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.