DEVELOPMENT OF PARAPOXVIRUS ORF VIRUS AS A VACCINE DELIVERY PLATFORM FOR USE IN SWINE

Abstract

Orf virus (ORFV) is the member of the parapoxvirus genus within the Poxviridae family. Efforts are being made to develop orf virus as a vaccine delivery platform for use in swine. The studies presented in this dissertation are aimed at developing orf virus-based vectored vaccines against different viral pathogens of swine and to improve the immunogenicity of the orf virus vector. Our previous studies have shown that ORFV recombinant expressing spike protein of porcine epidemic diarrhea virus (OV-PEDV-S) can provide protection to pigs from the virulent PEDV challenge. To further investigate if OV-PEDV-S recombinant can induce immunity in sows that is transferred to newborn piglets with the colostrum/milk and can protect the piglets against challenge infection with PEDV, an animal experiment was conducted where pregnant sows were immunized with OV-PEDV-S and piglets born from the immunized sows were challenged with PEDV. OV-PEDV-S was able to induce maternal immunity in piglets and there was significantly less mortality (<5% mortality) in the piglets born from the immunized sows when compared to the piglets born from non-immunized sows (50% mortality). Additionally, ORFV recombinants expressing hemagglutinin protein of influenza virus (OV-HA) and a recombinant expressing hemagglutinin and nucleoprotein of influenza virus (OV-HA-NP) were developed and their immunogenicity and protective efficacy was assessed in pigs. These recombinants induced robust humoral and cell-mediated immune response against swine influenza in pigs and when challenged with virulent H1N1 swine influenza virus, pigs immunized with OV-HA and OV-HA-NP were protected from the clinical disease. Another study was conducted to identify novel orf virus promoters using a transcriptomic approach. We demonstrate that an endogenous orf virus promoter, p116, leads to robust expression of heterologous genes in vitro. Overall, data presented in this paper provide evidence that orf virus could be an excellent vaccine delivery platform for use in swine. And the novel promoters identified here could improve the immunogenicity of ORFV recombinants by increasing the level of heterologous gene expression.