Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells

Scott Barbuto, Juliana Idoyaga, Miquel Vila-Perelló, Maria P. Longhi, Gaëlle Breton, Ralph M. Steinman, Tom W. Muir

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Targeted delivery of antigens to dendritic cells (DCs) is a promising vaccination strategy. However, to ensure immunity, the approach depends on coadministration of an adjuvant. Here we ask whether targeting of both adjuvant and antigen to DCs is sufficient to induce immunity. Using a protein ligation method, we develop a general approach for linking the immune stimulant, poly dA:dT (pdA:dT), to a monoclonal antibody (mAb) specific for DEC205 (DEC). We show that DEC-specific mAbs deliver pdA:dT to DCs for the efficient production of type I interferon in human monocyte-derived DCs and in mice. Notably, adaptive T-cell immunity is elicited when mAbs specific for DEC-pdA:dT are used as the activation stimuli and are administered together with a DC-targeted antigen. Collectively, our studies indicate that DCs can integrate innate and adaptive immunity in vivo and suggest that dual delivery of antigen and adjuvant to DCs might be an efficient approach to vaccine development.

Original languageEnglish (US)
Pages (from-to)250-256
Number of pages7
JournalNature Chemical Biology
Volume9
Issue number4
DOIs
StatePublished - Apr 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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