Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo

Plasmid-encoded DNA vaccines appear to be a safe and effective method for delivering antigen; however, the immunogenicity of such vaccines is often suboptimal. Cytokine adjuvants including interleukin (IL)-12, RANTES, granulocyte-macrophage colony-stimulating factor, IL-15, and others have been used to augment the immune response against DNA vaccines. In particular, IL-15 binds to a unique high-affinity receptor, IL-15Rα; is trans-presented to CD8+ T cells expressing the common βγ chain; and has been shown to play a role in the generation, maintenance, and proliferation of antigen-specific CD8+ T cells. In this study, we took the unique approach of using both a cytokine and its receptor as an adjuvant in an HIV-1 vaccine strategy. To study IL-15Rα expression, a unique monoclonal antibody (KK1.23) was generated to confirm receptor expression in vitro. Coimmunization of IL-15 and IL-15Rα plasmids with HIV-1 antigenic plasmids in mice enhanced the antigen-specific immune response 2-fold over IL-15 immunoadjuvant alone. Furthermore, plasmid-encoded IL-15Rα augments immune responses in the absence of IL-15, suggesting its role as a novel adjuvant. Moreover, pIL-15Rα enhanced the cellular, but not the humoral, immune response as measured by antigen-specific IgG antibody. This is the first report describing that IL-15Rα itself can act as an adjuvant by enhancing an antigen-specific T cell response. Uniquely, pIL-15 and pIL-15Rα adjuvants combined, but not the receptor α chain alone, may be useful as a strategy for generating and maintaining memory CD8+ T cells in a DNA vaccine