TY - JOUR
T1 - Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
AU - Velasquez, Lis Noelia
AU - Stüve, Philipp
AU - Gentilini, Maria Virginia
AU - Swallow, Maxine
AU - Bartel, Judith
AU - Lycke, Nils Yngve
AU - Barkan, Daniel
AU - Martina, Mariana
AU - Lujan, Hugo D.
AU - Kalay, Hakan
AU - van Kooyk, Yvette
AU - Sparwasser, Tim D.
AU - Berod, Luciana
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85043388902&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29662482
U2 - https://doi.org/10.3389/fimmu.2018.00471
DO - https://doi.org/10.3389/fimmu.2018.00471
M3 - Article
C2 - 29662482
SN - 1664-3224
VL - 9
SP - 471
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - MAR
M1 - 471
ER -