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.

中文翻译：

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在小鼠鼻内A（H1N1）pdm09流感疫苗接种中，聚肌苷酸-聚胞苷酸分子的双链结构可激发TLR3信号传导和佐剂活性。

聚肌苷酸-聚胞苷酸（PIC）是一种有效的双链RNA（dsRNA）佐剂，可用于鼻内流感疫苗接种。在小鼠中，对PIC的免疫应答的强度和持续时间与双链链长相关。避免PIC生产中PIC链扩展的合理方法是使用多个短poly（I）分子和一个长poly（C）分子进行PIC组装。在这项研究中，我们阐明了一种新开发的包含多个0.1 kb poly（I）分子和一个0.4 kb poly（C）分子的uPIC100-400分子，可通过阻止受攻击的病毒繁殖并诱导血凝素-来有效增强小鼠的免疫反应。鼻内接种A（H1N1）pdm09流感疫苗后，检测到特定的IgA。用多种短聚（I）分子制备的PIC的腹膜内毒性降低，表明uPIC100-400作为佐剂的有效范围扩大。与uPIC100-400相比，包含多个0.05 kb poly（I）分子的PIC分子未能引起小鼠粘膜免疫。这些结果与TLR3应答一致，但在细胞测定中与视黄酸诱导型基因I（RIG-1）样受体应答不一致，这表明PIC在小鼠鼻内免疫中的佐剂作用取决于TLR3信号传导。总之，本研究开发的毒性降低的双链PIC将有助于PIC佐剂疫苗的开发。05 kb poly（I）分子未能引起小鼠粘膜免疫。这些结果与TLR3应答一致，但在细胞测定中与视黄酸诱导型基因I（RIG-1）样受体应答不一致，这表明PIC在小鼠鼻内免疫中的佐剂作用取决于TLR3信号传导。总之，本研究开发的毒性降低的双链PIC将有助于PIC佐剂疫苗的开发。05 kb poly（I）分子未能引起小鼠粘膜免疫。这些结果与TLR3应答一致，但在细胞测定中与视黄酸诱导型基因I（RIG-1）样受体应答不一致，这表明PIC在小鼠鼻内免疫中的佐剂作用取决于TLR3信号传导。总之，本研究开发的毒性降低的双链PIC将有助于PIC佐剂疫苗的开发。