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.
Bibliography
Bonifaz, L. C., Bonnyay, D. P., Charalambous, A., Darguste, D. I., Fujii, S.-I., Soares, H., Brimnes, M. K., Moltedo, B., Moran, T. M., & Steinman, R. M. (2004). In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination. The Journal of Experimental Medicine, 199(6), 815â824.
Authors
10
- Laura C. Bonifaz (first)
- David P. Bonnyay (additional)
- Anna Charalambous (additional)
- Dara I. Darguste (additional)
- Shin-Ichiro Fujii (additional)
- Helena Soares (additional)
- Marie K. Brimnes (additional)
- Bruno Moltedo (additional)
- Thomas M. Moran (additional)
- Ralph M. Steinman (additional)
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Dates
Type | When |
---|---|
Created | 21 years, 5 months ago (March 15, 2004, 3:53 p.m.) |
Deposited | 2 years, 1 month ago (July 25, 2023, 8:37 a.m.) |
Indexed | 3 weeks, 5 days ago (Aug. 6, 2025, 8:23 a.m.) |
Issued | 21 years, 5 months ago (March 15, 2004) |
Published | 21 years, 5 months ago (March 15, 2004) |
Published Online | 21 years, 5 months ago (March 15, 2004) |
Published Print | 21 years, 5 months ago (March 15, 2004) |
@article{Bonifaz_2004, title={In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination}, volume={199}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20032220}, DOI={10.1084/jem.20032220}, number={6}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Bonifaz, Laura C. and Bonnyay, David P. and Charalambous, Anna and Darguste, Dara I. and Fujii, Shin-Ichiro and Soares, Helena and Brimnes, Marie K. and Moltedo, Bruno and Moran, Thomas M. and Steinman, Ralph M.}, year={2004}, month=mar, pages={815–824} }