title: In vivo assessment of equine arteritis virus vaccine improvement by disabling the deubiquitinase activity of papain-like protease 2.
abstract: Arteriviruses are a family of positive-stranded RNA viruses that includes the prototypic equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV). Although several vaccines against these viruses are commercially available there is room for improvement, especially in the case of PRRSV. The ability of arteriviruses to counteract the immune response is thought to decrease the efficacy of the current modified live virus vaccines. We have recently shown that the deubiquitinase (DUB) activity of EAV papain-like protease 2 (PLP2) is important for the inhibition of innate immune activation during infection. A vaccine virus lacking PLP2 DUB activity may therefore be more immunogenic and provide improved protection against subsequent challenge than its DUB-competent counterpart. To test this hypothesis, twenty Shetland mares were randomly assigned to one of three groups. Two groups were vaccinated, either with DUB-positive (n=9) or DUB-negative (n=9) recombinant EAV. The third group (n=2) was not vaccinated. All horses were subsequently challenged with the virulent KY84 strain of EAV. Both vaccine viruses proved to be replication competent in vivo. In addition, the DUB-negative virus provided a similar degree of protection against clinical disease as its DUB-positive parental counterpart. Owing to the already high level of protection provided by the parental virus, a possible improvement due to inactivation of PLP2 DUB activity could not be detected under these experimental conditions. Taken together, the data obtained in this study warrant further in vivo investigations into the potential of using DUB-mutant viruses for the improvement of arterivirus vaccines.
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Puck B
authors.initials: PB
authors.lastname: van Kasteren
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Robert C M
authors.initials: RC
authors.lastname: Knaap
authors.affiliation: MSD Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: van den Elzen
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Snijder
authors.affiliation: Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, 1400 Nicholasville Road, 40546-0099 Lexington, KY, USA.
authors.forename: Udeni B R
authors.initials: UB
authors.lastname: Balasuriya
authors.affiliation: MSD Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands.
authors.forename: Erwin
authors.initials: E
authors.lastname: van den Born
authors.affiliation: Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: m.kikkert@lumc.nl.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kikkert
mesh_terms: D000818:Animals; D018174:Arterivirus Infections / Q000517:prevention & control / Q000662:veterinary*; D000086882:Coronavirus Papain-Like Proteases; D007240:Equartevirus / Q000201:enzymology* / Q000276:immunology; D005260:Female; D006734:Horse Diseases / Q000517:prevention & control* / Q000821:virology*; D006736:Horses; D010206:Papain / Q000235:genetics*; D016896:Treatment Outcome; D064570:Ubiquitin-Specific Proteases / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use
chemical_list: D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D064570:Ubiquitin-Specific Proteases; D000086882:Coronavirus Papain-Like Proteases; D010206:Papain
keywords: Arterivirus; Deubiquitinase; EAV; Interferon; PRRSV; Vaccine