%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.