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Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV

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 contag...

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Autores principales: Diaz-San Segundo, Fayna, Medina, Gisselle N., Azzinaro, Paul, Gutkoska, Joseph, Mogulothu, Aishwarya, Attreed, Sarah E., Lombardi, Kimberly R., Shields, Jacob, Hudock, Teresa A., de los Santos, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131870/
https://www.ncbi.nlm.nih.gov/pubmed/34025625
http://dx.doi.org/10.3389/fmicb.2021.668890
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author Diaz-San Segundo, Fayna
Medina, Gisselle N.
Azzinaro, Paul
Gutkoska, Joseph
Mogulothu, Aishwarya
Attreed, Sarah E.
Lombardi, Kimberly R.
Shields, Jacob
Hudock, Teresa A.
de los Santos, Teresa
author_facet Diaz-San Segundo, Fayna
Medina, Gisselle N.
Azzinaro, Paul
Gutkoska, Joseph
Mogulothu, Aishwarya
Attreed, Sarah E.
Lombardi, Kimberly R.
Shields, Jacob
Hudock, Teresa A.
de los Santos, Teresa
author_sort Diaz-San Segundo, Fayna
collection PubMed
description 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.
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spelling pubmed-81318702021-05-20 Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV Diaz-San Segundo, Fayna Medina, Gisselle N. Azzinaro, Paul Gutkoska, Joseph Mogulothu, Aishwarya Attreed, Sarah E. Lombardi, Kimberly R. Shields, Jacob Hudock, Teresa A. de los Santos, Teresa Front Microbiol Microbiology 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. Frontiers Media S.A. 2021-05-05 /pmc/articles/PMC8131870/ /pubmed/34025625 http://dx.doi.org/10.3389/fmicb.2021.668890 Text en Copyright © 2021 Diaz-San Segundo, Medina, Azzinaro, Gutkoska, Mogulothu, Attreed, Lombardi, Shields, Hudock and de los Santos. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Diaz-San Segundo, Fayna
Medina, Gisselle N.
Azzinaro, Paul
Gutkoska, Joseph
Mogulothu, Aishwarya
Attreed, Sarah E.
Lombardi, Kimberly R.
Shields, Jacob
Hudock, Teresa A.
de los Santos, Teresa
Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV
title Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV
title_full Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV
title_fullStr Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV
title_full_unstemmed Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV
title_short Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV
title_sort use of protein pegylation to prolong the antiviral effect of ifn against fmdv
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131870/
https://www.ncbi.nlm.nih.gov/pubmed/34025625
http://dx.doi.org/10.3389/fmicb.2021.668890
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