| RRC ID |
62912
|
| 著者 |
Nakano T, Ohara Y, Fujita H, Ainai A, Yamamura ET, Suzuki T, Hasegawa H, Sone T, Asano K.
|
| タイトル |
Double-Stranded Structure of the Polyinosinic-Polycytidylic Acid Molecule to Elicit TLR3 Signaling and Adjuvant Activity in Murine Intranasal A(H1N1)pdm09 Influenza Vaccination.
|
| ジャーナル |
DNA Cell Biol
|
| 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.
|
| 巻・号 |
39(9)
|
| ページ |
1730-1740
|
| 公開日 |
2020-9-1
|
| DOI |
10.1089/dna.2019.5324
|
| PMID |
32580635
|
| MeSH |
Adjuvants, Immunologic / administration & dosage
Adjuvants, Immunologic / adverse effects
Adjuvants, Immunologic / therapeutic use*
Animals
Cells, Cultured
Female
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Immunoglobulin A / immunology
Influenza Vaccines / immunology
Interferon Inducers / administration & dosage
Interferon Inducers / adverse effects
Interferon Inducers / therapeutic use*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Orthomyxoviridae Infections / immunology*
Orthomyxoviridae Infections / prevention & control
Poly I-C / administration & dosage
Poly I-C / adverse effects
Poly I-C / therapeutic use*
Signal Transduction
Toll-Like Receptor 3 / metabolism*
Vaccination / methods*
|
| IF |
3.314
|
| リソース情報 |
| ヒト・動物細胞 |
MRC-5(RCB0218) |
