Abstract
Interferons (IFNs) are considered the first line of defense against viral diseases. Due to their ability to modulate immune responses, they have become an attractive therapeutic option to control virus infections. In fact, like many other viruses, foot-and-mouth disease virus (FMDV), the most contagious pathogen of cloven-hoofed animals, is highly sensitive to the action of IFNs. Previous studies demonstrated that type I, II, and III IFNs, expressed using a replication defective human adenovirus 5 (Ad5) vector, can effectively block FMDV replication in vitro and can protect animals when challenged 1 day after Ad5-IFN treatment, in some cases providing sterile immunity. Rapidly spreading foot-and-mouth disease (FMD) is currently controlled with vaccination, although development of a protective adaptive immune response takes 5–7 days. Therefore, an optimal strategy to control FMD outbreaks is to block virus replication and spread through sustained IFN activity while the vaccine-stimulated adaptive immune response is developed. Challenges with methods of delivery and/or with the relative short IFN protein half-life in vivo, have halted the development of such approach to effectively control FMD in the animal host. One strategy to chemically improve drug pharmacodynamics is the use of pegylation. In this proof-of-concept study, we demonstrate that pegylated recombinant porcine (po)IFNα displays strong and long-lasting antiviral activity against FMDV in vitro and in vivo, completely protecting swine against FMD for at least five days after a single dose. These results highlight the potential of this biotherapeutics to use in combination with vaccines to fully control FMD in the field.
Highlights
Foot-and-mouth disease (FMD) is a severe, highly contagious disease of cloven-hoofed animals including ruminants and swine
Pegylation of poIFNα Prolongs Antiviral Activity Against foot-and-mouth disease virus (FMDV) in vitro We have previously demonstrated that poIFNα expressed by using either, a replication defective human adenovirus 5 (Ad5-poIFNα) (Chinsangaram et al, 2003; Moraes et al, 2003, 2007) or a Venezuelan equine encephalitis (VEE) virus replicon particle (VRP-poIFNα) (Diaz-San Segundo et al, 2013), is very effective in blocking
While the antiviral activity of Ad5-expressed poIFNα waned by 3–4 dpt, a more sustained response was detected in cells treated with PEGpoIFNα which decreased by 4–6 dpt (Figure 1)
Summary
Foot-and-mouth disease (FMD) is a severe, highly contagious disease of cloven-hoofed animals including ruminants and swine. The disease is characterized by high fever and the appearance of vesicular lesions around the mouth, feet, and teats that resolve in a relative short time of approximately 2 weeks (Grubman and Baxt, 2004). Like other RNA viruses, FMDV has an error-prone polymerase that leads to a high mutation rate during genome replication and confers rapid adaptation on the virus. FMDV is antigenically variable and displays seven serotypes including A, O, C, Asia, and South African Territories (SAT) 1, 2, 3, and multiple subtypes (Knowles and Samuel, 2003). Such genetic plasticity and fast rate of replication are probably the drivers of high FMDV morbidity in over 70 species of ungulates
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
