TY - JOUR
T1 - Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells
AU - Barbuto, Scott
AU - Idoyaga, Juliana
AU - Vila-Perelló, Miquel
AU - Longhi, Maria P.
AU - Breton, Gaëlle
AU - Steinman, Ralph M.
AU - Muir, Tom W.
N1 - Funding Information:
The authors thank members of the Steinman and Muir laboratories for many valuable discussions. Funding was provided by National Institutes of Health Grants GM086868 (to T.W.M.), AI013013 (to R.M.S.), a Foundation for the National Institutes of Health Gates Foundation grant no. 334 (to R.M.S.) and a graduate fellowship to S. Barbuto by NIH MSTP grant GM07739.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
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U2 - 10.1038/nchembio.1186
DO - 10.1038/nchembio.1186
M3 - Article
C2 - 23416331
AN - SCOPUS:84875461861
SN - 1552-4450
VL - 9
SP - 250
EP - 256
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 4
ER -