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Cutting Edge: A Potent Adjuvant Effect of Ligand to Receptor Activator of NF-B Gene for Inducing Antigen-Specific CD8⁺ T Cell Response by DNA and Viral Vector Vaccination ¹

Yasushi Miyahira^2,*, Hisaya Akiba, Masaharu Katae^*,, Kaori Kubota, Seiki Kobayashi^¶, Tsutomu Takeuchi^¶, Adolfo García-Sastre^||, Yoshinosuke Fukuchi, Ko Okumura, Hideo Yagita and Takashi Aoki^*

Departments of ^* Molecular and Cellular Parasitology, Immunology, and Respiratory Medicine, Juntendo University School of Medicine, Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, and ^¶ Department of Tropical Medicine and Parasitology, Keio University School of Medicine, Tokyo, Japan; and ^|| Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029

The ligand to receptor activator of NF-B (RANK-L)/RANK interaction has been implicated in CD40 ligand/CD40-independent T cell priming by dendritic cells. In this report, we show that the coadministration of the RANK-L gene with a Trypanosoma cruzi gene markedly enhances the induction of Trypanosoma Ag-specific CD8⁺ T cells and improves the DNA vaccine efficacy. A similarly potent adjuvant effect of the RANK-L gene on the induction of Ag-specific CD8⁺ T cells was also observed when recombinant influenza virus expressing murine malaria Ag was used as an immunogen. In contrast, the coadministration of the CD40L gene was not effective in these systems. Our results demonstrated, for the first time, the potent immunostimulatory effect of the RANK-L gene to improve the CD8⁺ T cell-mediated immunity against infectious agents.

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