Plum Island Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Greenport, New York 11944, USA.
J Interferon Cytokine Res. 2011 Feb;31(2):227-36. doi: 10.1089/jir.2010.0055. Epub 2010 Sep 28.
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. Current inactivated vaccines require approximately 7 days to induce protection, but before this time vaccinated animals remain susceptible to disease. Previously, we demonstrated that intramuscular (IM) inoculation of a replication-defective human adenovirus type 5 (Ad5) vector containing a porcine interferon α gene (pIFNα) can protect swine challenged 1 day later by intradermal (ID) injection with FMDV A24 Cruzeiro from both clinical disease and virus replication. To extend these studies to other FMDV serotypes, we demonstrated the effectiveness of Ad5-pIFNα against ID challenge with O1 Manisa and Asia-1 and against A24 Cruzeiro in a direct contact challenge model. We also showed that an Ad5 vector containing the pIFNβ gene can protect swine against ID challenge with A24 Cruzeiro. Further, IM inoculation of a 10-fold lower dose of Ad5-pIFNα at 4 sites in the neck compared with 1 site in the hind limb can protect swine against ID challenge. These studies demonstrate the ability of Ad5-delivered type I IFN to rapidly protect swine against several FMDV serotypes and suggest that various modifications of this approach may enable this strategy to be successfully used in other FMD susceptible species.
口蹄疫病毒(FMDV)会引起偶蹄类动物的高度传染性疾病。目前的灭活疫苗大约需要 7 天才能产生保护作用,但在此之前,接种疫苗的动物仍然容易感染疾病。此前,我们已经证明,肌肉内(IM)接种含有猪干扰素 α 基因(pIFNα)的复制缺陷型人 5 型腺病毒(Ad5)载体可以通过皮内(ID)接种 FMDV A24 Cruzeiro 来保护猪,使其免受 1 天后的攻击,免受临床疾病和病毒复制的影响。为了将这些研究扩展到其他 FMDV 血清型,我们证明了 Ad5-pIFNα 对 O1 Manisa 和 Asia-1 的 ID 挑战以及对 A24 Cruzeiro 的直接接触挑战模型的有效性。我们还表明,含有 pIFNβ 基因的 Ad5 载体可以保护猪免受 A24 Cruzeiro 的 ID 挑战。此外,与后肢 1 个部位相比,在颈部 4 个部位肌肉内接种 10 倍低剂量的 Ad5-pIFNα 可以保护猪免受 ID 挑战。这些研究表明,Ad5 递送的 I 型 IFN 能够迅速保护猪免受多种 FMDV 血清型的侵害,并表明这种方法的各种改进可能使其能够成功用于其他易感 FMD 的物种。