Abstract: A member of the bovine type III IFN family, boIFN-?3, was identified and characterized. We expressed boIFN-?3 using a recombinant replication defective human adenovirus type 5 (Ad5) and demonstrated antiviral activity against foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus (VSV) in bovine cells in vitro. Cattle were inoculated with Ad5-boIFN-?3 followed by intradermolingual or aerosol FMDV challenge. Results demonstrated that the type III IFN family is conserved in bovines and that treatment of cattle with boIFN-?3 alone or in combination with IFN-? is able to confer delayed and reduced severity of FMD. Furthermore inoculation with Ad5-boIFN-?3 alone conferred full protection against aerosol challenge for at least 7 days after administration suggesting that type III IFN used in combination with FMD vaccines could fill one of the current gaps in emergency vaccination against FMDV.

Abstract: Previously we have identified a conserved domain (SAP, for SAF-A/B, Acinus, and PIAS) in the foot-and-mouth disease virus (FMDV) leader (L) protein coding region that is required for proper sub-cellular localization and function. Mutation of isoleucine 55 and leucine 58 to alanine (I55A, L58A) within the SAP domain resulted in a viable virus that displayed a mild attenuated phenotype in cell culture, along with altered sub-cellular distribution of L and failure to induce degradation of the transcription factor nuclear factor kappa-B. Here we report that inoculation of swine and cattle with this mutant virus results in the absence of clinical disease, the induction of a significant FMDV-specific neutralizing antibody response, and protection against subsequent homologous virus challenge. Remarkably, swine vaccinated with SAP mutant virus are protected against wild type virus challenge as early as two days post-vaccination suggesting that a strong innate as well as adaptive immunity is elicited.

Abstract: Interferons are the first line of defense against viral infections and administration of interferons as biotherapeutics has been demonstrated to be effective in controlling several viral infections. Here we report for the first time the identification and characterization of a member of the bovine type III IFN family, boIFN-?3. We have expressed boIFN-?3 using a recombinant replication defective human adenovirus type 5 (Ad5) and demonstrated antiviral activity against foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus (VSV) in bovine cells in vitro. Furthermore, we have tested the efficacy of boIFN-?3 against FMDV in vivo by inoculation of cattle with Ad5-boIFN-?3 followed by intradermolingual or aerosol virus challenge. Our results demonstrate that the type III IFN family is conserved in bovines and that treatment of cattle with boIFN-?3 alone or in combination with IFN-? is able to confer delayed and reduced severity of FMD.

Abstract: Previously we have identified a conserved domain (SAP, for SAF-A/B, Acinus, and PIAS) in the foot-and-mouth disease virus (FMDV) leader (L) protein coding region that is required for proper sub-cellular localization and function. Mutation of isoleucine 55 and leucine 58 to alanine (I55A, L58A) within the SAP domain resulted in a viable virus that displayed a mild attenuated phenotype in cell culture, along with altered sub-cellular distribution of L and failure to induce degradation of the transcription factor nuclear factor kappa-B. Here we report that inoculation of swine and cattle with this mutant virus results in the absence of clinical disease, the induction of a significant FMDV-specific neutralizing antibody response, and protection against subsequent homologous virus challenge. Remarkably, swine vaccinated with SAP mutant virus are protected against wild type virus challenge as early as two days post-vaccination suggesting that a strong innate as well as adaptive immunity is elicited.

Abstract: Previously, we showed that type I interferon (alpha/beta interferon [IFN-?/?]) can inhibit foot-and-mouth disease virus (FMDV) replication in cell culture, and swine inoculated with 109 PFU of human adenovirus type 5 expressing porcine IFN-? (Ad5-pIFN-?) were protected when challenged 1 day later. In this study, we found that type II pIFN (pIFN-?) also has antiviral activity against FMDV in cell culture and that, in combination with pIFN-?, it has a synergistic antiviral effect. We also observed that while each IFN alone induced a number of IFN-stimulated genes (ISGs), the combination resulted in a synergistic induction of some ISGs. To extend these studies to susceptible animals, we inoculated groups of swine with a control Ad5, 108 PFU of Ad5-pIFN-?, low- or high-dose Ad5-pIFN-?, or a combination of Ad5-pIFN-? and low- or high-dose Ad5-pIFN-? and challenged all groups with FMDV 1 day later.

Abstract: Previously, we showed that type I interferon (alpha/beta interferon [IFN-?/?]) can inhibit foot-and-mouth disease virus (FMDV) replication in cell culture, and swine inoculated with 109 PFU of human adenovirus type 5 expressing porcine IFN-? (Ad5-pIFN-?) were protected when challenged 1 day later. In this study, we found that type II pIFN (pIFN-?) also has antiviral activity against FMDV in cell culture and that, in combination with pIFN-?, it has a synergistic antiviral effect. We also observed that while each IFN alone induced a number of IFN-stimulated genes (ISGs), the combination resulted in a synergistic induction of some ISGs. To extend these studies to susceptible animals, we inoculated groups of swine with a control Ad5, 108 PFU of Ad5-pIFN-?, low- or high-dose Ad5-pIFN-?, or a combination of Ad5-pIFN-? and low- or high-dose Ad5-pIFN-? and challenged all groups with FMDV 1 day later.