Control of Foot-and-Mouth Disease When Vaccines are Not Available

Joseph M. Cummins
2018 Journal of Vaccines, Immunology and Immunopathology  
Commentary Vaccination and depopulation are the methods for control of Foot-and-Mouth Disease (FMD). Another tool is needed to manage FMD Virus (FMDV) if sero-type vaccines are unavailable. The USDA plans to vaccinate cattle if there is a major FMDV outbreak in the USA, but this plan is hampered by the lack of a stockpile of FMDV vaccines to treat millions of animals in a timely fashion. In the absence of FMDV specific vaccines strategies to induce or administer interferon (IFN) might limit
more » ... FN) might limit FMDV replication and disease in cattle and swine. A group of USDA Animal Research Service (ARS) scientists have reported that the FMDV establishes infection in susceptible cells/hosts by its ability to subvert key host defenses, specifically the inducible IFN response. FMDV inhibits production of IFN alpha (α) [l] and blocks a key IFNinducible, antiviral pathway, i.e.-Double-Stranded RNA (dsRNA) -dependent Protein Kinase R (PKR) [2]. Moreover, FMD Virion Protein 1 (VP1) has been specifically identified as a viral-origin IFN suppressor molecule by interacting with soluble resistancerelated calcium protein sorcin [3]. Since a key FMDV control method by host cells is suppression of IFNα production by FMDV-infected cells then exogenous treatment with IFNα or induction of endogenous IFN should help control FMD. Indeed, this vulnerability of FMDV to IFN has led to a novel viral disease control strategy using recombinant replication-defective human adenovirus 5 vector containing various species IFN genes. Results varied by species. ARS scientists reported that a human adenovirus type 5 vector containing porcine IFNα (Ad5-plFNα) injected into swine induced IFN production in these swine and completely protected them from FMD when challenged with virulent FMDV [4]. These swine remained FMD-asymptomatic, did not develop viremia nor did serum contain antibodies against viral nonstructural FMDV proteins. ARS scientists reported that Ad5-pIFNα given to pigs 1 to 5 but not 7 days prior to challenge with virulent FMDV were completely protected from FMD-disease. Pigs were protected even two days after IFN was no longer detected in the blood, likely because of the induction of IFN stimulated genes (ISG) [5,6]. This same research group reported that intramuscular (IM) injection of Ad5pIFNα protected swine against multiple serotypes of FMDV. IM inoculation of a 10-fold lower dose of Ad5-pIFNα at four sites in the neck compared with one site in the hind leg protected swine against FMDV challenge [7] . A fusion protein of porcine IFN regulatory factors (IRF) 7 and 3 delivered by an adenovirus vector [ad5-poIRF7/3(5D)] is an effective treatment to prevent FMD in swine. Animal pretreated with ad5-poIRF7/3(5D) 1 day before being exposed to FMDV and were completely protected from viral replication and clinical disease [8]. The doses of ad5-poIRF7/3(5D) required for protection were lower than those previously reported for similar approaches using Ad5 vectors delivering type I, II, or III IFN. When the Ad5-pIFNα vectored porcine IFN delivery system was injected into cattle, Ad5-pIFNα, provided partial in vivo protection by delaying viremia for one day and decreasing vesicle formulation [5] in challenged cattle. Subsequently, the ARS identified bovine IFN lambda-3 (boIFN-λ3) and demonstrated that expression of this molecule using recombinant replicationdefective human Ad5 vector, Ad5boIFN-λ3 exhibited F M D Vantiviral activity in vitro and in vivo. Inoculation of cattle with Ad5-boIFN λ3 induced systemic antiviral activity and up-regulation of ISG expression in the upper respiratory airways and the skin. ARS demonstrated that FMD disease could be delayed for at least 6 days when cattle were inoculated with Ad5-boIFN λ3 and challenged one day later with virulent FMDV. The delay in the appearance of disease was significantly prolonged when treated cattle were challenged by aerosol of FMDV; clinical signs of FMD-disease, viremia, or viral shedding in nasal swabs were not observed in Ad5-boIFN-λ3-treated cattle for at least nine days after challenge [9].
doi:10.29011/2575-789x.000131 fatcat:5pko6stj5jgo3k2g3hpntcuvay