Cutaneous delivery of Poly(dG) conjugated protein antigens targets and activates DCs in vivo. (130.38)

Abstract

Abstract Efficient and specific targeting of exogenous antigen to antigen presenting cells (APCs) in vivo is a critical challenge for vaccine design. APCs acquire antigens from a variety of sources and endocytic mechanisms can predetermine intracellular antigen routing, processing and presentation to CD4+ or CD8+ T cells. We have designed an APC targeting strategy based on simple and direct coupling of Poly(dG) oligo deoxynucleotides to protein antigens. In comparison to soluble OVA, we find that conjugates of Poly(dG) and OVA (OVA-Poly(dG)) are rapidly internalized by dendritic cells (DCs) and follow distinct intracellular processing pathways. Functionally, OVA-Poly(dG) is both presented to OVA-specific CD4+ T cells (OT-II cells) and efficiently cross-presented to OVA-specific CD8+ T cells (OT-I cells) by DCs in vitro. Importantly, immunization of naïve animals by direct injection of OVA-Poly(dG) results in efficient priming of potent antigen specific CTL responses. Extending our findings to human skin, we show that I.D. injection of antigen-Poly(dG) conjugates results in efficient uptake by human skin migratory DCs including Langerin+ DCs that also acquire potent T cell allostimulatory function. Our data suggest that Poly(dG) can both target antigens to human skin immune APCs and function as an adjuvant to induce potent CD4 and CD8 mediated T cell immunity.