Novel immunization strategies: Aptamer-targeted antigen delivery

Abstract

Dendritic cells (DCs) play a crucial role in stimulating adaptive immunity, and targeting antigen delivery via DC-specific cell surface receptors has emerged as a promising means for enhancing vaccination to infectious disease and neoplasms. In particular, targeting antigen to the DC receptor DEC205 induces antigen presentation to CD4+ T cells and cross-presentation to CD8+ T cells.;Because nucleic acid aptamers are chemically synthesized, they may constitute an easier to produce, more functionally extensible alternative to the currently dominant antibody-based approaches. In order to explore the antigen-delivery capabilities of nucleic acid aptamers, we have selected, cloned, and minimized an RNA aptamer with high affinity and specificity to the mouse DEC205 protein. We demonstrate that aptamer that is chemically conjugated to the model antigen ovalbumin (OVA) enhances OVA antigen delivery to murine CD11c+ splenocytes in vitro, as evidenced by OT-I proliferation and production of cytokines interferon gamma (IFNgamma) and interleukin 2 (IL-2).;We have begun exploring the parameters necessary for effective in vivo antigen delivery. Strong, though not aptamer-specific, stimulation of adoptively transferred OT-I cells is achieved with subcutaneous co-injection of polyinosinic-polycytidylic acid (poly(I:C)) with RNA-OVA conjugates. Aptamer-specific OT-I stimulation requires additional poly(I:C) pretreatment. While our aptamer-based approach does not currently appear to immunize as effectively as antibody-based approaches, this work serves as proof-of-principle for aptamer-specific receptor-targeted antigen delivery.