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Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses

Journal article
Authors L. N. Velasquez
P. Stuve
M. V. Gentilini
M. Swallow
J. Bartel
Nils Y Lycke
D. Barkan
M. Martina
H. D. Lujan
H. Kalay
Y. van Kooyk
T. D. Sparwasser
L. Berod
Published in Frontiers in Immunology
Volume 9
ISSN 1664-3224
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links https://doi.org/10.3389/fimmu.2018....
Keywords DC-specific-ICAM3-grabbing-nonintegrin, tuberculosis, vaccine, dendritic cells, Ag85B, cd4 t-cells, c-type lectin, bovis bcg-vaccination, dc-sign, in-vivo, protective immunity, dec-205 receptor, infection, mice, induction, Immunology
Subject categories Immunology

Abstract

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-gamma(+) IL-2(+) TNF-alpha(+) 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.

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