Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944, USA.
J Interferon Cytokine Res. 2012 Oct;32(10):462-73. doi: 10.1089/jir.2012.0012. Epub 2012 Aug 27.
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. Vaccines require ∼7 days to induce protection; thus, before this time, vaccinated animals are still susceptible to the disease. Our group has previously shown that swine inoculated with 1×10(11) focus forming units (FFU) of a replication-defective human adenovirus containing the gene for porcine interferon alpha (Adt-pIFN-α) are sterilely protected from FMDV serotypes A24, O1 Manisa, or Asia 1 when the animals are challenged 1 day postadministration, and protection can last for 3-5 days. Polyriboinosinic-polyribocytidylic acid stabilized with poly-l-lysine and carboxymethyl cellulose (poly ICLC) is a synthetic double-stranded RNA that is a viral mimic and activates multiple innate immune pathways through interaction with toll-like receptor 3 and MDA-5. It is a potent inducer of IFNs. In this study, we initially examined the effect of poly IC and IFN-α on FMDV replication and gene induction in cell culture. Poly ICLC alone or combined with Adt-pIFN-α was then evaluated for its therapeutic efficacy in swine against intradermal challenge with FMDV A24, 1 day post-treatment. Groups of swine were subcutaneously inoculated either with poly ICLC alone (4 or 8 mg) or in combination with different doses of Adt-pIFN-α (2.5×10(9), 1×10(9), or 2.5×10(8) FFU). While different degrees of protection were achieved in all the treated animals, a dose of 8 mg of poly ICLC alone or combined with 1×10(9) FFU of Adt-pIFN-α was sufficient to sterilely protect swine when challenged 24 h later with FMDV A24. IFN-stimulated gene (ISG) expression in peripheral blood mononuclear cells at 1 day post-treatment was broader and higher in protected animals than in nonprotected animals. These data indicate that poly ICLC is a potent stimulator of IFN and ISGs in swine and at an adequate dose is sufficient to induce complete protection against FMD.
口蹄疫病毒（FMDV）会引起偶蹄动物的高度传染性疾病。疫苗需要大约 7 天才能产生保护作用；因此，在此之前，接种疫苗的动物仍然容易感染该疾病。我们的研究小组此前曾表明，接种 1×10(11)个复制缺陷型人腺病毒（包含猪干扰素-α基因）的猪，在接种后第 1 天受到 FMDV 血清型 A24、O1 Manisa 或 Asia 1 的攻击时，可完全免受感染，保护期可持续 3-5 天。多聚肌苷酸-多聚胞苷酸与聚赖氨酸和羧甲基纤维素稳定化（poly ICLC）是一种合成的双链 RNA，是一种病毒模拟物，通过与 toll 样受体 3 和 MDA-5 相互作用，激活多种先天免疫途径。它是干扰素的有效诱导剂。在这项研究中，我们首先研究了 poly IC 和 IFN-α对细胞培养中 FMDV 复制和基因诱导的影响。然后评估了 poly ICLC 单独或与 Adt-pIFN-α联合使用对猪的治疗效果，在接种 FMDV A24 后第 1 天进行治疗。将猪皮下接种 poly ICLC（4 或 8mg）或与不同剂量的 Adt-pIFN-α（2.5×10(9)、1×10(9)或 2.5×10(8)FFU）联合接种。虽然所有接受治疗的动物都获得了不同程度的保护，但单独使用 8mg poly ICLC 或与 1×10(9)FFU 的 Adt-pIFN-α联合使用，在接种 FMDV A24 后 24 小时后即可对猪进行无菌保护。在接种治疗后第 1 天，保护性动物外周血单核细胞中干扰素刺激基因（ISG）的表达更广泛且更高。这些数据表明，poly ICLC 是猪干扰素和 ISG 的有效刺激物，在足够的剂量下足以诱导对 FMD 的完全保护。
