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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Agriculture / Faculty of Agriculture >
Peer-reviewed Journal Articles, etc >
Double-Stranded Structure of the Polyinosinic-Polycytidylic Acid Molecule to Elicit TLR3 Signaling and Adjuvant Activity in Murine Intranasal A(H1N1)pdm09 Influenza Vaccination
| Title: | Double-Stranded Structure of the Polyinosinic-Polycytidylic Acid Molecule to Elicit TLR3 Signaling and Adjuvant Activity in Murine Intranasal A(H1N1)pdm09 Influenza Vaccination |
| Authors: | Nakano, Tetsuo Browse this author | | Ohara, Yuki Browse this author | | Fujita, Hiroshi Browse this author | | Ainai, Akira Browse this author | | Yamamura, Ei-Tora Browse this author | | Suzuki, Tadaki Browse this author | | Hasegawa, Hideki Browse this author | | Sone, Teruo Browse this author | | Asano, Kozo Browse this author |
| Keywords: | poly(I | | C) | | double-stranded structure | | intranasal vaccination | | mucosal adjuvant | | immune toxicity | | TLR3 |
| Issue Date: | 4-Sep-2020 |
| Publisher: | Mary Ann Liebert |
| Journal Title: | DNA and Cell Biology |
| Volume: | 39 |
| Issue: | 9 |
| Start Page: | 1730 |
| End Page: | 1740 |
| Publisher DOI: | 10.1089/dna.2019.5324 |
| Abstract: | Polyinosinic-polycytidylic acid (PIC) is a potent double-stranded RNA (dsRNA) adjuvant useful in intranasal influenza vaccination. In mice, the intensity and duration of immune responses to PIC correlated with the double-stranded chain length. A rational method to avoid PIC chain extension in PIC production is to use multiple short poly(I) molecules and one long poly(C) molecule for PIC assembly. In this study, we elucidate that a newly developed uPIC100-400 molecule comprising multiple 0.1 kb poly(I) molecules and one 0.4 kb poly(C) molecule effectively enhanced the immune responses in mice, by preventing the challenged viral propagation and inducing hemagglutinin-specific IgA, after intranasal A(H1N1)pdm09 influenza vaccination. Reduced intraperitoneal toxicity of PIC prepared with multiple short poly(I) molecules in mice indicates the widened effective range of uPIC100-400 as an adjuvant. In contrast to uPIC100-400, the PIC molecule comprising multiple 0.05 kb poly(I) molecules failed to elicit mouse mucosal immunity. These results were consistent with TLR3 response but not retinoic acid inducible gene I (RIG-I)-like receptor response in the cell assays, which suggests that the adjuvant effect of PIC in mouse intranasal immunization depends on TLR3 signaling. In conclusion, the double-stranded PIC with reduced toxicity developed in this study would contribute to the development of PIC-adjuvanted vaccines. |
| Rights: | Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/dna.2019.5324 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/82612 |
| Appears in Collections: | 農学院・農学研究院 (Graduate School of Agriculture / Faculty of Agriculture) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 浅野 行蔵
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