Orf virus: A promising new therapeutic agent

Abstract

Summary The orf virus (ORFV) is a zoonotic, epitheliotropic, DNA parapoxvirus that infects principally sheep and goats. Exposure of animals to the virus or immunization by an ORFV preparation can accentuate the severity of disease, which has provoked an interest in the underlying cellular, virological, and molecular mechanisms. The identified ORFV virulence genes and the fact that the virus can repeatedly infect a host, owing to its evasive mechanisms, contribute to the development of potent immune modulators in various animal species. ORFV has been developed as a vaccine in veterinary medicine. The unique host immune‐evasion ability of ORFV has made it an important candidate for vaccine vectors and biological agents (as an oncolytic virus). Genetic modifications using ORFV to obtain safe and efficient preparations and mechanistic studies are improvements to the currently available methods for disease treatment.

Selection of chromatographic methods for the purification of cell culture-derived Orf virus for its application as a vaccine or viral vector

“…Previously, we reported the successful use of the attenuated ORFV for the generation of different recombinants with diverse modifications able to protect against various infectious viral diseases ( Rohde et al, 2011 , 2013 ; Rziha et al, 2016 ; van Rooij et al, 2010 ). Also other ORFV strains were successfully used for the generation of recombinant vaccines ( Hain et al, 2016 ; Tan et al, 2012 ), and inactivated ORFV showed immunomodulatory properties in different preclinical models ( Bergqvist et al, 2017 ; Fleming et al, 2015 ; Wang et al, 2019 ). Furthermore, Rintoul et al demonstrated an oncolytic activity for the wild-type ORFV strain NZ2, causing a significantly reduced tumor growth in immune-competent and xenograft human tumor models ( Rintoul et al, 2012 ).…”

“…Knowledge on ORFV production processes is very limited and mainly focuses on upstream processing ( Pohlscheidt et al, 2008 ; Wang et al, 2019 ). Downstream processing (DSP) procedures generally employ sucrose gradient ultracentrifugation ( Rziha et al, 2016 ) and do not satisfy regulatory demands for the purity of vaccines and gene therapeutic products ( European Pharmacopoeia, 2020 ; World Health Organization, 2017 ).…”

Inhibition of orf virus replication in goat skin fibroblast cells by the HSPA1B protein, as demonstrated by iTRAQ-based quantitative proteome analysis

“…Genes involved in virulence and pathogenesis are distributed in the ITR regions of the ORFV genome. The virus encodes involved in immunomodulation, including viral-interleukin 10 (vIL-10, ORFV127), vascular endothelial growth factor (VEGF, ORFV132), orf virus interferon resistance protein (OVIFNR, ORFV020), chemokine binding protein (CBP, ORFV112), granulocyte-macrophage colony-stimulating factor/interleukin-2 (GM-CSF/IL-2) inhibitory protein (GIF, ORFV117), nuclear factor kappa B (NF-κB) inhibitory protein (ORFV125), and deoxyuridine 5′-triphosphate pyrophosphatase (dUTPase, ORFV007) [38].…”

Recombinant Modified Vaccinia Virus Ankara (MVA) Vaccines Efficiently Protect Cockatiels Against Parrot Bornavirus Infection and Proventricular Dilatation Disease

“…In addition, a newly generated set of Orf virus (ORFV; family Poxviridae) vector vaccines [18] expressing PaBV-4 N and P was included. ORFV-based recombinant vector vaccines have been successfully applied in a broad range of species [19][20][21], including efficient protection of rats against experimental BoDV-1 infection [13,22].…”