Intradermal immunization with polyguanine conjugated antigens enables targeted and sustained delivery of protein antigens to dendritic cells in vivo. (APP3P.111)

Abstract

Abstract Effective vaccine design depends on the ability to target specific antigens to antigen presenting cells (APCs), including dendritic cells (DCs). Conjugation of proteins antigens to polyguanine (Poly(dG)) molecules is a novel immunization approach capable of transforming soluble antigens into aggregated particulates with exposed scavenger receptor (SR) ligands. We have previously shown that Poly(dG) conjugation to protein antigen results in increased antigen-specific helper and cytotoxic T cell responses, memory T cell induction, and antibody titers. Here, we specifically investigate mechanisms of Poly(dG)-conjugated antigen delivery and internalization. Compared to soluble OVA, Poly(dG)-OVA is rapidly and more efficiently internalized by bone marrow derived DCs in vitro, and this internalization is inhibited by scavenger receptor blockade. Importantly, in a mouse model intradermally injected Poly(dG)-OVA results in antigen persistence in the skin for up to 7 days. This is accompanied by increased antigen uptake by skin resident DCs and persistent migration of antigen loaded DCs to the draining lymph nodes. DCs exposed to Poly(dG)-OVA had increased expression of CCR7 and secretion of MCP-1, TNF-α, and IL-6. These results suggest that coupling Poly(dG) to protein antigens enables efficient DC targeting through SRs, prolonged delivery of antigens in vivo, and activation of innate immunity. This approach may be used to design more efficient antiviral and antitumor vaccines.