Double-Stranded Structure of the Polyinosinic-Polycytidylic Acid Molecule to Elicit TLR3 Signaling and Adjuvant Activity in Murine Intranasal A(H1N1)pdm09 Influenza Vaccination
| Autor: | Teruo Sone, Tetsuo Nakano, Ei-Tora Yamamura, Yuki Ohara, Hideki Hasegawa, Tadaki Suzuki, Kozo Asano, Akira Ainai, Hiroshi Fujita |
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| Rok vydání: | 2020 |
| Předmět: |
endocrine system
double-stranded structure Interferon Inducers medicine.medical_treatment Hemagglutinin Glycoproteins Influenza Virus C) Biology Mice chemistry.chemical_compound Immune system Adjuvants Immunologic Orthomyxoviridae Infections immune toxicity Genetics medicine Animals TLR3 Molecular Biology Cells Cultured Mice Inbred BALB C Vaccination RNA mucosal adjuvant Cell Biology General Medicine biochemical phenomena metabolism and nutrition intranasal vaccination Virology Immunoglobulin A Toll-Like Receptor 3 Mice Inbred C57BL RNA silencing Poly I-C poly(I chemistry Influenza Vaccines Polyinosinic:polycytidylic acid Female Nasal administration Adjuvant Signal Transduction |
| Zdroj: | DNA and Cell Biology. 39:1730-1740 |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2019.5324 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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