title: Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells.
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.
authors: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York, USA.
authors: Scott
authors: S
authors: Barbuto
authors: Juliana
authors: J
authors: Idoyaga
authors: Miquel
authors: M
authors: Vila-Perelló
authors: Maria P
authors: MP
authors: Longhi
authors: Gaëlle
authors: G
authors: Breton
authors: Ralph M
authors: RM
authors: Steinman
authors: Tom W
authors: TW
authors: Muir
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015703:Antigens, CD / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D016503:Drug Delivery Systems; D005822:Genetic Vectors; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D010957:Plasmids; D011067:Poly dA-dT / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; C093569:DEC-205 receptor; D018796:Immunoconjugates; D007370:Interferon Type I; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011067:Poly dA-dT