title: A porcine reproductive and respiratory syndrome virus candidate vaccine based on the synthetic attenuated virus engineering approach is attenuated and effective in protecting against homologous virus challenge.
abstract: Current porcine reproductive and respiratory syndrome virus (PRRSV) vaccines sometimes fail to provide adequate immunity to protect pigs from PRRSV-induced disease. This may be due to antigenic differences among PRRSV strains. Rapid production of attenuated farm-specific homologous vaccines is a feasible alternative to commercial vaccines. In this study, attenuation and efficacy of a codon-pair de-optimized candidate vaccine generated by synthetic attenuated virus engineering approach (SAVE5) were tested in a conventional growing pig model. Forty pigs were vaccinated intranasally or intramuscularly with SAVE5 at day 0 (D0). The remaining 28 pigs were sham-vaccinated with saline. At D42, 30 vaccinated and 19 sham-vaccinated pigs were challenged with the homologous PRRSV strain VR2385. The experiment was terminated at D54. The SAVE5 virus was effectively attenuated as evidenced by a low magnitude of SAVE5 viremia for 1-5 consecutive weeks in 35.9% (14/39) of the vaccinated pigs, lack of detectable nasal SAVE5 shedding and failure to transmit the vaccine virus from pig to pig. By D42, all vaccinated pigs with detectable SAVE5 viremia also had detectable anti-PRRSV IgG. Anti-IgG positive vaccinated pigs were protected from subsequent VR2385 challenge as evidenced by lack of VR2385 viremia and nasal shedding, significantly reduced macroscopic and microscopic lung lesions and significantly reduced amount of PRRSV antigen in lungs compared to the non-vaccinated VR2385-challenged positive control pigs. The nasal vaccination route appeared to be more effective in inducing protective immunity in a larger number of pigs compared to the intramuscular route. Vaccinated pigs without detectable SAVE5 viremia did not seroconvert and were fully susceptible to VR2385 challenge. Under the study conditions, the SAVE approach was successful in attenuating PRRSV strain VR2385 and protected against homologous virus challenge. Virus dosage likely needs to be adjusted to induce replication and protection in a higher percentage of vaccinated pigs.
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Evenson
authors.affiliation: The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
authors.forename: P F
authors.initials: PF
authors.lastname: Gerber
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Xiao
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Halbur
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ni
authors.affiliation: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: X J
authors.initials: XJ
authors.lastname: Meng
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA; The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK. Electronic address: Tanja.Opriessnig@roslin.ed.ac.uk.
authors.forename: T
authors.initials: T
authors.lastname: Opriessnig
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D007273:Injections, Intramuscular; D009666:Nose / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D034421:Sus scrofa; D013552:Swine; D064166:Vaccine Potency; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014766:Viremia; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: Attenuation; Efficacy; Porcine reproductive and respiratory syndrome virus (PRRSV); Synthetic attenuated virus engineering (SAVE); Vaccine