In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination

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 ant...

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Veröffentlicht in:The Journal of experimental medicine 2004-03, Vol.199 (6), p.815-824
Hauptverfasser: Bonifaz, Laura C, Bonnyay, David P, Charalambous, Anna, Darguste, Dara I, Fujii, Shin-Ichiro, Soares, Helena, Brimnes, Marie K, Moltedo, Bruno, Moran, Thomas M, Steinman, Ralph M
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20032220