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

By L. Bonifaz, D. Bonnyay, A. Charalambous, Dara I. Darguste, S. Fujii, Helena Soares, M. Brimnes, Bruno Moltedo, T. Moran, R. Steinman. Journal of Experimental Medicine, 2004

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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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/95c846df1dbcc5f06e18b9360992117db2d7a4e1

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Citations in the corpus

Signalling through C-type lectin receptors: shaping immune responses (2009, background): “In these studies, targeting of DeC205 by antibodies did not result in DC maturation and therefore induced tolerance in the absence of an adjuvant such as CD40 or TLR ligands (for example CpG-containing DNA or polyinosinic-polycytidylic acid) 76 .”
Cancer immunotherapy via dendritic cells (2012, neutral): “Ralph Steinman and colleagues demonstrated that the specific targeting of antigens to DCs in vivo elicits potent antigen-specific CD4 + and CD8 + T cell-mediated immunit”
Dendritic cells as therapeutic vaccines against cancer (2005, background): “By contrast, concomitant activation of these DCs with CD40-specific antibody results in a potent immune response, because the DCs are induced to express a large number of co-stimulatory molecule”
Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting (2007, background): “By contrast, co-administration of DC maturation stimuli with targeted OVA leads to a strong induction of OVA-specific CD4 + and CD8 + T-cell response”
The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells (2010, methodology): “This consisted of the quality control assessment using the AffyPLM package (Bolstad et al., 2004; e.g., visual examination of hybridization chip images, relative log expression, and normalized unscaled standard errors plots) and the robust multichip analysis normalization (Irizarry et al., 2003)…”
Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response (2013, background): “For instance, targeting antigens to DEC-205 using monoclonal antibodies induced tolerance under noninflammatory conditions but mediated immunogenicity under activating conditions by cluster of differentiation 40 ligand (CD40L) (3).”
From Vaccines to Memory and Back (2010, positive): “The importance of studies addressing the role of different DC and monocytes subsets in T cell responses cannot be overemphasized in view of the possibility of targeting antigens and vaccines to different cell types in vivo (Bonifaz et al., 2004; Kamphorst et al., 2010).”