In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination

Laura C. Bonifaz, David P. Bonnyay, Anna Charalambous, Dara I. Darguste, Shin Ichiro Fujii, Helena Soares, Marie K. Brimnes, Bruno Moltedo, Thomas M. Moran, Ralph M. Steinman

Research output: Contribution to journalArticlepeer-review

760 Scopus citations

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 α-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 αDEC-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.

Original languageEnglish
Pages (from-to)815-824
Number of pages10
JournalJournal of Experimental Medicine
Volume199
Issue number6
DOIs
StatePublished - 15 Mar 2004

Keywords

  • CD8 T cell
  • DEC-205 receptor
  • Dendritic cell
  • Immunotherapy
  • Vaccination

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