title: Development of a porcine reproductive and respiratory syndrome virus-like-particle-based vaccine and evaluation of its immunogenicity in pigs.
abstract: Porcine reproductive and respiratory syndrome (PRRS) is a leading cause of economic burden to the pork industry worldwide. The routinely used modified live PRRS virus vaccine (PRRS-MLV) induces clinical protection, but it has safety concerns. Therefore, in an attempt to develop a safe and protective inactivated PRRSV vaccine, we generated PRRS-virus-like-particles (PRRS-VLPs) containing the viral surface proteins GP5-GP4-GP3-GP2a-M or GP5-M using a novel baculovirus expression system. Our in vitro results indicated that the desired PRRSV proteins were incorporated in both the VLPs preparations based on their reactivity in immunogold electron microscopy and ELISA. To boost their immunogenicity in pigs, we entrapped the PRRS-VLPs in PLGA nanoparticles and coadministered them intranasally with a potent adjuvant. We then evaluated their efficacy in pigs against a viral challenge using a virulent heterologous field isolate. Our results indicated that PRRS-VLPs induced an anamnestic immune response, since we observed boosted IgG and IFN-γ production in vaccinated and virus-challenged animals, but not during the pre-challenge period. Importantly, a two-log reduction in the lung viral load was detected in PRRS-VLP-vaccinated animals. In conclusion, we generated PRRS-VLPs containing up to five viral surface proteins and demonstrated their immunogenicity in pigs, but further studies are required to improve its immunogenicity and efficacy as a vaccine candidate.
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Basavaraj
authors.initials: B
authors.lastname: Binjawadagi
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Yashavanth Shaan
authors.initials: YS
authors.lastname: Lakshmanappa
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Longchao
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Dhakal
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Hiremath
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Ouyang
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Duan-Liang
authors.initials: DL
authors.lastname: Shyu
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Jesus
authors.initials: J
authors.lastname: Arcos
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Shang
authors.initials: S
authors.lastname: Pengcheng
authors.affiliation: Aptimmune Biologics Inc., Champaign, IL, 61820, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Gilbertie
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL, 61802, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Zuckermann
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
authors.forename: Daral
authors.initials: D
authors.lastname: Jackwood
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA. gourapura.1@osu.edu.
authors.forename: Gourapura J
authors.initials: GJ
authors.lastname: Renukaradhya
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005814:Genes, Viral; D008168:Lung / Q000276:immunology / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000276:immunology*; D034421:Sus scrofa; D013552:Swine; D015164:Vaccines, Inactivated / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D015164:Vaccines, Inactivated; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; D014765:Viral Vaccines