Tazaki Taiyu, Tabata Koshiro, Ainai Akira, Ohara Yuki, Kobayashi Shintaro, Ninomiya Takafumi, Orba Yasuko, Mitomo Hideyuki, Nakano Tetsuo, Hasegawa Hideki, Ijiro Kuniharu, Sawa Hirofumi, Suzuki Tadaki, Niikura Kenichi
Graduate School of Chemical Sciences and Engineering, Hokkaido University Sapporo 060-8628 Japan.
Department of Pathology, National Institute of Infectious Diseases Toyama 1-23-1, Shinjuku-ku Tokyo 162-8640 Japan
RSC Adv. 2018 May 4;8(30):16527-16536. doi: 10.1039/c8ra01690a. eCollection 2018 May 3.
Intranasal inactivated influenza vaccines can elicit mucosal immune responses that protect against virus infection. For the development of intranasal inactivated influenza vaccines, effective adjuvants inducing minimal adverse reactions are required. Generally, however, lower toxicity adjuvants have lower adjuvanticity. In this research, we fabricated nanoparticle-based adjuvants to enhance its adjuvanticity. Herein, we focused on low-molecular-weight polyinosinic-polycytidylic acid, referred to as uPIC(40:400), as a weak and less toxic RNA adjuvant. We conjugated uPIC(40:400) with different shaped gold nanoparticles (AuNPs) electrostatically. Conjugation with gold nanorods, but not spherical AuNPs, markedly enhanced the adjuvanticity of uPIC(40:400), leading to the suppression of viral infection in mice. Notably, conjugation with gold nanorods did not increase the inflammatory cytokine production in dendritic cells. These data indicated that gold nanorods can provide a good platform for enhancing the weak adjuvanticity of uPIC(40:400) while maintaining low inflammatory cytokine production toward the development of intranasal inactivated influenza vaccines.
鼻内灭活流感疫苗可引发黏膜免疫反应，从而预防病毒感染。对于鼻内灭活流感疫苗的研发而言，需要能诱导最小不良反应的有效佐剂。然而，一般来说，毒性较低的佐剂其佐剂活性也较低。在本研究中，我们制备了基于纳米颗粒的佐剂以增强其佐剂活性。在此，我们将低分子量聚肌苷酸-聚胞苷酸（称为uPIC(40:400)）作为一种弱毒性且毒性较小的RNA佐剂进行研究。我们通过静电作用将uPIC(40:400)与不同形状的金纳米颗粒（AuNPs）偶联。与金纳米棒而非球形AuNPs偶联，显著增强了uPIC(40:400)的佐剂活性，从而抑制了小鼠体内的病毒感染。值得注意的是，与金纳米棒偶联并未增加树突状细胞中炎性细胞因子的产生。这些数据表明，金纳米棒可为增强uPIC(40:400)的弱佐剂活性提供一个良好的平台，同时在鼻内灭活流感疫苗的研发中保持低水平的炎性细胞因子产生。
