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

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.

Stuve, P. (author)
Gentilini, M. V. (author)
Swallow, M. (author)
Bartel, J. (author)
Lycke, Nils Y,1954Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xlycni (author)
Barkan, D. (author)
Martina, M. (author)
Lujan, H. D. (author)
Kalay, H. (author)
van Kooyk, Y. (author)
Sparwasser, T. D. (author)
Berod, L. (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för mikrobiologi och immunologi (creator_code:org_t)

By the author/editor: Velasquez, L. N.; Stuve, P.; Gentilini, M. V.; Swallow, M.; Bartel, J.; Lycke, Nils Y, 1 ...; show more...; Barkan, D.; Martina, M.; Lujan, H. D.; Kalay, H.; van Kooyk, Y.; Sparwasser, T. D ...; Berod, L.; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Immunology

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