Influenza A virus (IAV) causes significant losses to the swine industry. Here we constructed a novel attenuated live IAV vaccine designed to elicit an immune response to conserved IAV proteins by removal of the highly variable hemagglutinin gene. A unique feature of this strategy was the ability of our engineered IAV vaccine to express protein derived from porcine epidemic diarrhea virus (PEDV). Laboratory characterization of the constructed IAV/PEDV vaccine strain found that the virus was capable of robust growth and expressed the PEDV S1 protein. Following two doses of vaccine delivered to pigs intranasally, pigs were challenged with PEDV or IAV to assess protection afforded by the vaccine. Analysis of sera collected from vaccinated pigs found that the vaccine failed to induce a measurable immune response. Likewise, analysis of IAV and PEDV shedding from pigs found no evidence for protection and suggested a possible enhancement of disease. Widespread severe clinical disease due to Streptococcus suis was manifest immediately following initial vaccination and may have adversely affected the immune system’s ability to respond to the vaccine. Likewise, a number of viral co-infections were identified from the pigs during the experiment which may have adversely impacted vaccine performance.
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