Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle
Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1360397/full |
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| author | Sarah E. Attreed Christina Silva Monica Rodriguez-Calzada Monica Rodriguez-Calzada Aishwarya Mogulothu Aishwarya Mogulothu Sophia Abbott Sophia Abbott Paul Azzinaro Peter Canning Lillian Skidmore Jay Nelson Nick Knudsen Gisselle N. Medina Gisselle N. Medina Teresa de los Santos Fayna Díaz-San Segundo Fayna Díaz-San Segundo |
| author_facet | Sarah E. Attreed Christina Silva Monica Rodriguez-Calzada Monica Rodriguez-Calzada Aishwarya Mogulothu Aishwarya Mogulothu Sophia Abbott Sophia Abbott Paul Azzinaro Peter Canning Lillian Skidmore Jay Nelson Nick Knudsen Gisselle N. Medina Gisselle N. Medina Teresa de los Santos Fayna Díaz-San Segundo Fayna Díaz-San Segundo |
| author_sort | Sarah E. Attreed |
| collection | DOAJ |
| description | Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system’s first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection—usually only 1–3 days post-treatment (dpt)—diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios. |
| first_indexed | 2024-04-24T13:51:18Z |
| format | Article |
| id | doaj.art-3ee70f9a70464224baed98e2e52dc037 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-24T13:51:18Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-3ee70f9a70464224baed98e2e52dc0372024-04-04T04:48:49ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-04-011510.3389/fmicb.2024.13603971360397Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattleSarah E. Attreed0Christina Silva1Monica Rodriguez-Calzada2Monica Rodriguez-Calzada3Aishwarya Mogulothu4Aishwarya Mogulothu5Sophia Abbott6Sophia Abbott7Paul Azzinaro8Peter Canning9Lillian Skidmore10Jay Nelson11Nick Knudsen12Gisselle N. Medina13Gisselle N. Medina14Teresa de los Santos15Fayna Díaz-San Segundo16Fayna Díaz-San Segundo17Plum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesOak Ridge Institute for Science and Education Plum Island Animal Disease Center Research Participation Program, Oak Ridge, TN, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesDepartment of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesAnimal Biosciences and Biotechnology Laboratory, Northeast Area, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesVetBio Partners, LLC., Carmel, IN, United StatesAmbrx Biopharma, Inc., La Jolla, CA, United StatesAmbrx Biopharma, Inc., La Jolla, CA, United StatesAmbrx Biopharma, Inc., La Jolla, CA, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesNational Bio-and Agro-Defense Facility, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Manhattan, KS, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesPlum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United StatesOffice of Biodefense, Research Resources and Translational Research, National Institute of Allergy and Infectious Disease, Rockville, MD, United StatesFoot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system’s first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection—usually only 1–3 days post-treatment (dpt)—diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1360397/fullFMDVfoot-and-mouth diseasetype III interferonIFNIFNλ3IL28B |
| spellingShingle | Sarah E. Attreed Christina Silva Monica Rodriguez-Calzada Monica Rodriguez-Calzada Aishwarya Mogulothu Aishwarya Mogulothu Sophia Abbott Sophia Abbott Paul Azzinaro Peter Canning Lillian Skidmore Jay Nelson Nick Knudsen Gisselle N. Medina Gisselle N. Medina Teresa de los Santos Fayna Díaz-San Segundo Fayna Díaz-San Segundo Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle Frontiers in Microbiology FMDV foot-and-mouth disease type III interferon IFN IFNλ3 IL28B |
| title | Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle |
| title_full | Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle |
| title_fullStr | Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle |
| title_full_unstemmed | Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle |
| title_short | Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle |
| title_sort | prophylactic treatment with pegylated bovine ifnλ3 effectively bridges the gap in vaccine induced immunity against fmd in cattle |
| topic | FMDV foot-and-mouth disease type III interferon IFN IFNλ3 IL28B |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1360397/full |
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