Successes and challenges in the developmemt of baculovirus-based vaccines for swine influenza and porcine circovirus type 2b

Abstract

<p>Respiratory disease is a major cause of economic losses for the swine industry and ranks as a primary contributor to mortality in swine. Over the last 20 years, as swine production operations have continued to consolidate, respiratory disease in swine has become increasingly multifactorial in nature. The work presented in this dissertation centers around the development of vaccines utilizing the baculovirus expression vector system (BEVS) for two viral pathogens associated with the Porcine Respiratory Disease Complex (PRDC), a multifactorial respiratory disease syndrome affecting growing and finishing phase pigs. The work in this dissertation demonstrates that vaccines formulated with subunit hemagglutinin (HA) fused to an IgG Fc domain, VLP-displayed HA, or baculovirus-displayed HA may be viable alternatives to the traditional inactivated whole virus approaches currently utilized in the veterinary vaccine industry. In addition, this work uncovers a potential problem for the development of VLP-based porcine circovirus type 2 (PCV2) vaccines as an ORF2 protein from an emerging PCV2b strain was found to have dramatically reduced yields of VLP when expressed using the BEVS. Furthermore, the work in this dissertation demonstrates that a single amino acid mutation can be used to overcome this loss of VLP yield and that the mutated ORF2 protein provides protective efficacy against a PCV2b challenge in pigs.</p>