The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response. Polyinosinic-polycytidylic (Poly(I:C)) is a synthetic double-stranded RNA (dsRNA) that can engage Toll-like receptor 3 (TLR3) to initiate immune responses. However, the Poly(I:C)-induced toxicity and inefficient delivery prevent its applications. In our study, combination adjuvants are formulated by aluminum oxyhydroxide nanorods (AlOOH NRs) and Poly(I:C), named Al-Poly(I:C), and the covalent interaction between the two components is further demonstrated. Al-Poly(I:C) mediates enhanced humoral and cellular immune responses in three antigen models, HBsAg virus-like particles (VLPs), human papilloma virus (HPV) VLPs and varicella-zoster virus (VZV) glycoprotein E (gE). Further mechanistic studies demonstrate that the dose and molecular weight (MW) of Poly(I:C) determine the physicochemical properties and adjuvanticity of the Al-Poly(I:C) combination adjuvants. Al-Poly(I:C) with higher Poly(I:C) dose promotes antigen-bearing dendritic cells (DCs) recruitment and B cells proliferation in lymph nodes. Al-Poly(I:C) formulated with higher MW Poly(I:C) induces higher activation of helper T cells, B cells, and CTLs. This study demonstrates that Al-Poly(I:C) potentiates the humoral and cellular responses in vaccine formulations. It offers insights for adjuvant design to meet the formulation requirements in both prophylactic and therapeutic vaccines.

中文翻译：

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用于预防性疫苗的具有平衡免疫刺激潜力的羟基氧化铝-聚(I:C)组合佐剂


高纯度抗原的开发促进了对能够触发高水平免疫反应的新型佐剂的迫切需求。 Polyinosinic-polycytidylic (Poly(I:C)) 是一种合成的双链 RNA (dsRNA)，可以与 Toll 样受体 3 (TLR3) 结合以启动免疫反应。然而，Poly(I:C) 引起的毒性和低效的传递阻碍了其应用。在我们的研究中，由羟基氧化铝纳米棒（AlOOH NRs）和Poly（I：C）配制组合佐剂，命名为Al-Poly（I：C），并进一步证明了两种组分之间的共价相互作用。 Al-Poly(I:C) 在 HBsAg 病毒样颗粒 (VLP)、人乳头瘤病毒 (HPV) VLP 和水痘带状疱疹病毒 (VZV) 糖蛋白 E (gE) 三种抗原模型中介导增强的体液和细胞免疫应答。进一步的机理研究表明，Poly(I:C) 的剂量和分子量 (MW) 决定了 Al-Poly(I:C) 组合佐剂的理化性质和佐剂作用。 Al-Poly(I:C) 与较高 Poly(I:C) 剂量可促进淋巴结中携带抗原的树突状细胞 (DC) 募集和 B 细胞增殖。 Al-Poly(I:C) 与较高 MW Poly(I:C) 配制而成，可诱导辅助 T 细胞、B 细胞和 CTL 的更高活化。这项研究表明 Al-Poly(I:C) 可以增强疫苗配方中的体液和细胞反应。它为佐剂设计提供了见解，以满足预防性和治疗性疫苗的配方要求。