title: In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination.
abstract: The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic alpha-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the alphaDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell-mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bonifaz
authors.forename: David P
authors.initials: DP
authors.lastname: Bonnyay
authors.forename: Anna
authors.initials: A
authors.lastname: Charalambous
authors.forename: Dara I
authors.initials: DI
authors.lastname: Darguste
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Fujii
authors.forename: Helena
authors.initials: H
authors.lastname: Soares
authors.forename: Marie K
authors.initials: MK
authors.lastname: Brimnes
authors.forename: Bruno
authors.initials: B
authors.lastname: Moltedo
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Moran
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019013:CD40 Antigens; C093569:DEC-205 receptor; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D010047:Ovalbumin