Polyguanine-conjugated antigens for scavenger receptor targeting and self-adjuvanting vaccines (VAC13P.1125)

Abstract We have recently developed a novel vaccine strategy that involves conjugating antigens to polyguanine sequences to fabricate aggregated particulates with exposed scavenger receptor ligands for in vivo targeting to antigen presenting cells. We have previously demonstrated that polyguanine-conjugated ovalbumin (Poly(dG)-OVA) leads to enhanced antigen-specific T cell and antibody responses. In this study, we show that exposing dendritic cells (DCs) to Poly(dG)-OVA results in increased antigen internalization that is inhibited by scavenger receptor ligands. Further, DCs internalizing Poly(dG)-OVA complexes exhibit increased cytokine secretion and inflammatory marker expression. In vivo, intradermal injection of Poly(dG)-OVA results in complex persistence in the skin for up to 7 days. Intradermally immunized mice demonstrated increased immune infiltrates in the skin and a persistent inflammatory cytokine profile. In these immunized animals, Poly(dG)-OVA particles reach the draining lymph nodes directly and in association with migratory DCs. We further demonstrate that Poly(dG)-OVA immunization of mice with established OVA-expressing melanoma tumors exhibited delayed tumor growth and improved survival. Taken together, these results suggest that immunization with polyguanine-conjugated antigens can induce more effective antitumor immunity by targeting DCs through scavenger receptors and inducing proinflammatory DC activation.