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

LC Bonifaz, DP Bonnyay, A Charalambous… - The Journal of …, 2004 - rupress.org
LC Bonifaz, DP Bonnyay, A Charalambous, DI Darguste, SI Fujii, H Soares, MK Brimnes…
The Journal of experimental medicine, 2004rupress.org
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 …
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.
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