Porcine Type I Interferon Rapidly Protects Swine Against Challenge with Multiple Serotypes of Foot-and-Mouth Disease Virus

Abstract

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.

Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

“…Thus far, we have demonstrated that inoculation of mice with VRP-GFP induced a strong protective antiviral response against FMDV which correlated with increased levels of IFN-␣ in serum. This is in accordance with the demonstrated antiviral and protective effect of type I IFN against FMDV in the natural host (4,9,10). To confirm the antiviral effect of IFN-␣ against FMDV in the mouse model, we treated groups of five mice with 10 4 U of muIFN-␣ followed by challenge with 5 ϫ 10 4 PFU of FMDV A24 at 4 or 18 h after treatment.…”

“…As we previously demonstrated, administration of Ad5-poIFN-␣ sterilely protected swine from FMDV infection (10). Since our results in cell culture indicate that VRPs containing an IFN gene induce an enhanced protective response and higher levels of ISGs than VRP-GFP treatment, we plan to initiate studies in naturally susceptible animals with different doses of VRP-po/ boIFN-␣/␤ and examine their efficacy against FMDV challenge.…”

“…We have previously demonstrated that swine inoculated with Ad5-poIFN-␣ are rapidly protected when challenged 1 day later with FMDV (4,9,10). More recently we also showed that treatment of bovines with Ad5-boIFN-3 can significantly delay and reduce clinical disease (12).…”

“…Protection can last for 3 to 5 days (4). We further showed that this approach is also protective against several other FMDV serotypes, e.g., O1, Manisa, and Asia-1 (10). However, when this approach was used to rapidly protect cattle, we found that only one of six treated animals did not develop vesicular lesions; although all of the other treated animals developed disease, it was delayed and less severe than that in control animals (11).…”

“…We have shown that FMDV replication is inhibited by prior treatment of cells with interferon type I (IFN-␣/␤), II, or III (6)(7)(8). Based on this information, we constructed Ad5 vectors containing porcine type I IFN genes (Ad5-poIFN-␣/␤) and demonstrated that swine inoculated with Ad5-poIFN-␣/␤ are protected from challenge with FMDV A24 Cruzeiro as early as 1 day after Ad5-poIFN-␣/␤ administration (4,9,10). Protection can last for 3 to 5 days (4).…”