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Title: Investigation of porcine interferons as a metaphylactic intervention against classical swine fever virus
Author: Crudgington, Bentley
ISNI:       0000 0004 7658 134X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Classical Swine Fever (CSF) is an important viral disease of swine. The application of Interferon (IFN) via viral vectors could be a beneficial intervention strategy against CSFV. Unlike type I and II IFN, the anti-CSFV activity of type III IFNs is unknown. Type III IFNs have similar antiviral actions to type I IFNs, but their specific receptors have limited tissue distribution and may be important as very early defences against infection at epithelial surfaces. PoIFN (type I (α, β) type II (γ) and type III (λ1, 3)) were cloned into a mammalian expression vector, expressed in porcine tracheal (NpTr) cells and the induction of an immune response and anti-CSFV activity examined. PoIFNs were subsequently expressed using adenovirus and MVA viral vectors and their antiviral activity assessed. All three types of vectored IFN upregulated expression of the interferon stimulated gene MxA and significantly reduced CSFV infection in the NpTr cell line and in porcine primary cells. Inoculation of NpTr cells with adenovirus and MVA vectors expressing all three types of IFN inhibited CSFV infection, with the Ad_IFNα/β and λ constructs inducing a greater anti- CSFV effect than the Ad_IFNγ constructs. Intranasal and intramuscular inoculations with MVA vectors did not induce ISG upregulation in the tonsils or protect monocytes against an ex vivo CSFV challenge. These outcomes are not likely to be true reflections on the potential of this vector system due to limitations in the preparation of inoculum. Intranasal inoculation with adeno vectors expressing type I and type III IFN did not induce any significant systemic or tissue specific antiviral responses and under these conditions would not be predicted to offer successful protection against CSFV infection. Intramuscular inoculation of Ad_IFNα into pigs induced upregulated serum IFNα levels and offered significant levels of protection against ex vivo CSFV challenge of isolated leukocytes and offers a promising candidate for metaphylactic intervention.
Supervisor: Skinner, Mike ; Everett, Helen ; Crooke, Helen Sponsor: Animal and Plant Health Agency (APHA)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral