The Journal of Experimental Medicine
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Published 15 March 2004. doi:10.1084/jem.20032220
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 6, 815-824
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In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination

Laura C. Bonifaz1, David P. Bonnyay1, Anna Charalambous1, Dara I. Darguste1, Shin-Ichiro Fujii1, Helena Soares1, Marie K. Brimnes2, Bruno Moltedo2, Thomas M. Moran2, and Ralph M. Steinman1

1 Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
2 Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029

Address correspondence to Ralph M. Steinman, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021-6399. Phone: (212) 327-8106; Fax: (212) 327-8875; email: Steinma{at}mail.rockefeller.edu

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 {alpha}DEC-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.

Key Words: dendritic cell • DEC-205 receptor • vaccination • CD8 T cell • immunotherapy

Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; MESNA, 2-mercaptoethanesulfonic acid sodium salt; OVA, ovalbumin.


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