Type III interferon protects swine against foot-and-mouth disease

In recent years, we have developed novel strategies to control foot-and-mouth disease (FMD), including the use of biotherapeutics such as interferons (IFN) delivered by a replication-defective human adenovirus type 5 (Ad5). Swine can be sterilely protected after vaccination with an Ad5 that encodes porcine type I IFN (poIFN-α), and cattle can be similarly protected or develop significantly reduced disease when treated with an Ad5 delivering bovine type III IFN (boIFN-λ3). Here, we have evaluated the efficacy of porcine IFN-λ3 (poIFN-λ3) against FMD virus in vivo. Swine inoculated with different doses of Ad5-poIFN-λ3 were protected against disease in a dose-dependent manner. Despite the absence of systemic antiviral activity, 7 out of 10 Ad5-poIFN-λ3 inoculated animals did not develop disease or viremia, and the other 3 inoculated animals displayed delayed and milder disease by 7 days postchallenge as compared with control animals inoculated with an Ad5 control vector. While analysis of gene expression showed significant induction of IFN and IFN-stimulated genes in Ad5-poIFN-λ3-treated cultured porcine epithelial kidney cells, there was limited gene induction in peripheral blood monocytes isolated from treated swine. These results suggest that treatment with Ad5-poIFN-λ3 is an effective biotherapeutic strategy against FMD in swine.