| Autor: |
Zhao D; Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba 305-0047, Japan., Tu ATT; Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba 305-0047, Japan.; Division of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo 060-0808, Japan.; Department of Magnetic and Biomedical Materials, Faculty of Materials Science and Technology, University of Science, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City 70000, Vietnam.; Ho Chi Minh City Campus, Vietnam National University, Linh Trung Ward, Thu Duc City, Ho Chi Minh City 70000, Vietnam., Shobo M; Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba 305-0047, Japan., Le NBT; Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba 305-0047, Japan.; Division of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo 060-0808, Japan., Yoshikawa C; Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba 305-0047, Japan., Sugai K; School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino-shi, Tokyo 180-8602, Japan., Hakamata Y; School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino-shi, Tokyo 180-8602, Japan., Yamazaki T; Research Center for Functional Materials (RCFM), National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba 305-0047, Japan.; Division of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo 060-0808, Japan. |
| Abstrakt: |
Unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) induce inflammatory cytokines and type I interferons (IFNs) to activate the immune system. To apply CpG ODNs as vaccine adjuvants, the cellular uptake and stability of phosphodiester-based, non-modified ODNs require further improvement. Previously developed new CpG ODNs forming guanine-quadruplex (G4) structures showed higher nuclease resistance and cellular uptake than linear CpG ODNs; however, the complex formation of G4-CpG ODNs with antigen proteins is necessary for their application as vaccine adjuvants. In this study, we utilized a cationic polymer, ε-poly- L -lysine (ε-PLL), as a carrier for G4-CpG ODNs and antigen. The ε-PLL/G4-CpG ODN complex exhibited enhanced stability against nucleases. Cellular uptake of the ε-PLL/G4-CpG ODN complex positively correlated with the N/P ratio. In comparison to naked G4-CpG ODNs, the ε-PLL/G4-CpG ODN complex induced extremely high levels of interleukin (IL)-6, IL-12, and IFN-β. Relative immune cytokine production was successfully tuned by N/P ratio modification. Mice with the ε-PLL/G4-CpG ODN/ovalbumin (OVA) complex showed increased OVA-specific immunoglobulin (Ig)G, IgG1, and IgG2c levels, whereas total IgE levels did not increase and weight gain rates were not affected. Therefore, ε-PLL can serve as a safe and effective phosphodiester-based, non-modified CpG ODN delivery system, and the ε-PLL/G4-CpG ODN/antigen complex is a highly promising candidate for vaccine adjuvants and can be further used in clinical research. |
