Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle

Attreed, Sarah E.; Silva, Christina; Rodriguez-Calzada, Monica; Mogulothu, Aishwarya; Abbott, Sophia; Azzinaro, Paul; Canning, Peter; Skidmore, Lillian; Nelson, Jay; Knudsen, Nick; Medina, Gisselle N.; de los Santos, Teresa; Díaz-San Segundo, Fayna

doi:10.3389/fmicb.2024.1360397

Title: Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle

Journal Article · 04 April 2024 · Frontiers in Microbiology

DOI: https://doi.org/10.3389/fmicb.2024.1360397 · OSTI ID:2471350

Attreed, Sarah E. ^[1]; Silva, Christina ^[1]; Rodriguez-Calzada, Monica ^[2]; Mogulothu, Aishwarya ^[3]; Abbott, Sophia ^[4]; Azzinaro, Paul ^[1]; Canning, Peter ^[5]; Skidmore, Lillian ^[6]; Nelson, Jay ^[6]; Knudsen, Nick ^[6]; Medina, Gisselle N. ^[7]; de los Santos, Teresa ^[1]; Díaz-San Segundo, Fayna ^[8]

US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS)
US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); Univ. of Connecticut, Storrs, CT (United States)
US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); US Dept. of Agriculture (USDA), Beltsville, MD (United States). Agricultural Research Service (ARS)
VetBio Partners, LLC., Carmel, IN (United States)
Ambrx Biopharma, Inc., La Jolla, CA (United States)
US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); US Dept. of Agriculture (USDA), Manhattan, KS (United States). Agricultural Research Service (ARS)
US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); National Institute of Allergy and Infectious Disease, Rockville, MD (United States)

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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471350

Journal Information:: Frontiers in Microbiology, Journal Name: Frontiers in Microbiology Vol. 15; ISSN 1664-302X

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

References (80)

Antiviral activity of porcine interferon omega 7 against foot‐and‐mouth disease virus in vitro Li, Shi‐Fang; Zhao, Fu‐Rong; Gong, Mei‐Jiao Journal of Medical Virology, Vol. 91, Issue 2 https://doi.org/10.1002/jmv.25272	journal	November 2018
Prolonged Circulation Half-life of Interferon γ Activity by Gene Delivery of Interferon γ–Serum Albumin Fusion Protein in Mice Miyakawa, Noriko; Nishikawa, Makiya; Takahashi, Yuki Journal of Pharmaceutical Sciences, Vol. 100, Issue 6 https://doi.org/10.1002/jps.22473	journal	June 2011
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method Livak, Kenneth J.; Schmittgen, Thomas D. Methods, Vol. 25, Issue 4 https://doi.org/10.1006/meth.2001.1262	journal	December 2001
Effects of stress on immune function: the good, the bad, and the beautiful Dhabhar, Firdaus S. Immunologic Research, Vol. 58, Issue 2-3 https://doi.org/10.1007/s12026-014-8517-0	journal	May 2014
Function of CD80 and CD86 on monocyte- and stem cell-derived dendritic cells Dilioglou, Smaroula; Cruse, Julius M.; Lewis, Robert E. Experimental and Molecular Pathology, Vol. 75, Issue 3 https://doi.org/10.1016/S0014-4800(03)00072-8	journal	December 2003
Validation of an Mx/CAT reporter gene assay for the quantification of bovine type-I interferon Fray, M. D.; Mann, G. E.; Charleston, B. Journal of Immunological Methods, Vol. 249, Issue 1-2 https://doi.org/10.1016/S0022-1759(00)00359-8	journal	March 2001
Foot-and-mouth disease virus Domingo, Esteban; Baranowski, Eric; Escarmı́s, Cristina Comparative Immunology, Microbiology and Infectious Diseases, Vol. 25, Issue 5-6 https://doi.org/10.1016/S0147-9571(02)00027-9	journal	October 2002
CD40 ligand-dependent signaling of bovine B lymphocyte development and differentiation Estes, D. M.; Brown, W. C.; Hirano, A. Veterinary Immunology and Immunopathology, Vol. 63, Issue 1-2 https://doi.org/10.1016/S0165-2427(98)00077-4	journal	May 1998
FMD vaccines Doel, T. R. Virus Research, Vol. 91, Issue 1 https://doi.org/10.1016/S0168-1702(02)00261-7	journal	January 2003
Innate immune responses following emergency vaccination against foot-and-mouth disease virus in pigs Rigden, R. C.; Carrasco, C. P.; Barnett, P. V. Vaccine, Vol. 21, Issue 13-14 https://doi.org/10.1016/S0264-410X(02)00663-1	journal	March 2003
A recombinant adenovirus bicistronically expressing porcine interferon-α and interferon-γ enhances antiviral effects against foot-and-mouth disease virus Kim, Su-Mi; Kim, Se-Kyung; Park, Jong-Hyeon Antiviral Research, Vol. 104 https://doi.org/10.1016/j.antiviral.2014.01.014	journal	April 2014
Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju Antiviral Research, Vol. 143 https://doi.org/10.1016/j.antiviral.2017.01.018	journal	July 2017
Detection of Viral Infections by Innate Immunity Carty, Michael; Guy, Coralie; Bowie, Andrew G. Biochemical Pharmacology, Vol. 183 https://doi.org/10.1016/j.bcp.2020.114316	journal	January 2021
Antiviral effects of selected IMPDH and DHODH inhibitors against foot and mouth disease virus Mei-jiao, Gong; Shi-fang, Li; Yan-yan, Chang Biomedicine & Pharmacotherapy, Vol. 118 https://doi.org/10.1016/j.biopha.2019.109305	journal	October 2019
Shared and Distinct Functions of Type I and Type III Interferons Lazear, Helen M.; Schoggins, John W.; Diamond, Michael S. Immunity, Vol. 50, Issue 4 https://doi.org/10.1016/j.immuni.2019.03.025	journal	April 2019
Antiviral activity of porcine interferon delta 8 against foot-and-mouth disease virus in vitro Li, Shi-fang; Shao, Jun-jun; Zhao, Fu-rong International Immunopharmacology, Vol. 59 https://doi.org/10.1016/j.intimp.2018.03.022	journal	June 2018
Infection Dynamics of Foot-and-Mouth Disease Virus in Cattle Following Intranasopharyngeal Inoculation or Contact Exposure Pacheco, J. M.; Stenfeldt, C.; Rodriguez, L. L. Journal of Comparative Pathology, Vol. 155, Issue 4 https://doi.org/10.1016/j.jcpa.2016.08.005	journal	November 2016
Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1 Naeem, Zahra; Raza, Sohail; Afzal, Saba Microbial Pathogenesis, Vol. 155 https://doi.org/10.1016/j.micpath.2021.104914	journal	June 2021
Foot-and-mouth disease virus (FMDV) leader proteinase negatively regulates the porcine interferon-λ1 pathway Wang, Dang; Fang, Liurong; Liu, Lizhi Molecular Immunology, Vol. 49, Issue 1-2 https://doi.org/10.1016/j.molimm.2011.09.009	journal	October 2011
Increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2B is associated with a specific T cell response Moraes, Mauro Pires; Segundo, Fayna Diaz-San; Dias, Camila C. Vaccine, Vol. 29, Issue 51 https://doi.org/10.1016/j.vaccine.2011.10.037	journal	November 2011
An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine Alejo, Diana M.; Moraes, Mauro P.; Liao, Xiaofen Vaccine, Vol. 31, Issue 18 https://doi.org/10.1016/j.vaccine.2013.02.060	journal	April 2013
Testing the modularity of the N-terminal amphipathic helix conserved in picornavirus 2C proteins and hepatitis C NS5A protein Teterina, Natalya L.; Gorbalenya, Alexander E.; Egger, Denise Virology, Vol. 344, Issue 2 https://doi.org/10.1016/j.virol.2005.08.044	journal	January 2006
Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication O'Donnell, Vivian; Pacheco, Juan M.; LaRocco, Michael Virology, Vol. 410, Issue 1 https://doi.org/10.1016/j.virol.2010.10.042	journal	February 2011
Antiviral activity of bovine type III interferon against foot-and-mouth disease virus Díaz-San Segundo, Fayna; Weiss, Marcelo; Perez-Martín, Eva Virology, Vol. 413, Issue 2 https://doi.org/10.1016/j.virol.2011.02.023	journal	May 2011
Combination of Adt-O1Manisa and Ad5-boIFNλ3 induces early protective immunity against foot-and-mouth disease in cattle Diaz-San Segundo, Fayna; Montiel, Nestor A.; Sturza, Diego F. Virology, Vol. 499 https://doi.org/10.1016/j.virol.2016.09.027	journal	December 2016
Identification of the role of RIG-I, MDA-5 and TLR3 in sensing RNA viruses in porcine epithelial cells using lentivirus-driven RNA interference Hüsser, Linda; Alves, Marco P.; Ruggli, Nicolas Virus Research, Vol. 159, Issue 1 https://doi.org/10.1016/j.virusres.2011.04.005	journal	July 2011
What's the difference between CD80 and CD86? Sansom, David M.; Manzotti, Claire N.; Zheng, Yong Trends in Immunology, Vol. 24, Issue 6 https://doi.org/10.1016/s1471-4906(03)00111-x	journal	June 2003
A Comparison of different routes of inoculation of cattle for detection of the virus of foot-and-mouth disease Henderson, W. M. Journal of Hygiene, Vol. 50, Issue 2 https://doi.org/10.1017/S0022172400019537	journal	June 1952
IL-28, IL-29 and their class II cytokine receptor IL-28R Sheppard, Paul; Kindsvogel, Wayne; Xu, Wenfeng Nature Immunology, Vol. 4, Issue 1 https://doi.org/10.1038/ni873	journal	December 2002
IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex Kotenko, Sergei V.; Gallagher, Grant; Baurin, Vitaliy V. Nature Immunology, Vol. 4, Issue 1 https://doi.org/10.1038/ni875	journal	December 2002
Decoding type I and III interferon signalling during viral infection Mesev, Emily V.; LeDesma, Robert A.; Ploss, Alexander Nature Microbiology, Vol. 4, Issue 6 https://doi.org/10.1038/s41564-019-0421-x	journal	April 2019
ISG15 in antiviral immunity and beyond Perng, Yi-Chieh; Lenschow, Deborah J. Nature Reviews Microbiology, Vol. 16, Issue 7 https://doi.org/10.1038/s41579-018-0020-5	journal	May 2018
Expanding the genetic code Wang, Lei; Schultz, Peter G. Chemical Communications, Issue 1 https://doi.org/10.1039/b108185n	journal	December 2001
Cloning, expression and biological function of the bovine CD40 homologue:‘qc role in B‐lymphocyte growth and differentiation in cattle‘pa Hirano, A.; Brown, W. C.; Estes, D. M. Immunology, Vol. 90, Issue 2 https://doi.org/10.1046/j.1365-2567.1997.00159.x	journal	February 1997
Cross‐presentation of cell‐associated antigens by CD8α⁺ dendritic cells is attributable to their ability to internalize dead cells Schulz, Oliver; Reis e. Sousa, Caetano Immunology, Vol. 107, Issue 2 https://doi.org/10.1046/j.1365-2567.2002.01513.x	journal	October 2002
A general approach to site-specific antibody drug conjugates Tian, Feng; Lu, Yingchun; Manibusan, Anthony Proceedings of the National Academy of Sciences, Vol. 111, Issue 5 https://doi.org/10.1073/pnas.1321237111	journal	January 2014
Immunoregulatory properties of ISG15, an interferon-induced cytokine. D'Cunha, J.; Knight, E.; Haas, A. L. Proceedings of the National Academy of Sciences, Vol. 93, Issue 1 https://doi.org/10.1073/pnas.93.1.211	journal	January 1996
Long-acting Growth Hormones Produced by Conjugation with Polyethylene Glycol Clark, Ross; Olson, Kenneth; Fuh, Germaine Journal of Biological Chemistry, Vol. 271, Issue 36 https://doi.org/10.1074/jbc.271.36.21969	journal	September 1996
Adenovirus-Mediated Type I Interferon Expression Delays and Reduces Disease Signs in Cattle Challenged with Foot-and-Mouth Disease Virus Wu, Qiaohua; Brum, Mario C. S.; Caron, Luizinho Journal of Interferon & Cytokine Research, Vol. 23, Issue 7 https://doi.org/10.1089/107999003322226014	journal	July 2003
Pulmonary Administration of Interferon Beta-1a-Fc Fusion Protein in Non-Human Primates Using an Immunoglobulin Transport Pathway Vallee, Sebastien; Rakhe, Swapnil; Reidy, Thomas Journal of Interferon & Cytokine Research, Vol. 32, Issue 4 https://doi.org/10.1089/jir.2011.0048	journal	April 2012
Type III Interferon Protects Swine Against Foot-and-Mouth Disease Perez-Martin, Eva; Diaz-San Segundo, Fayna; Weiss, Marcelo Journal of Interferon & Cytokine Research, Vol. 34, Issue 10 https://doi.org/10.1089/jir.2013.0112	journal	October 2014
CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle Carr, B. V.; Lefevre, E. A.; Windsor, M. A. Journal of General Virology, Vol. 94, Issue Pt_1 https://doi.org/10.1099/vir.0.045732-0	journal	October 2012
The ultrastructure of the developing replication site in foot-and-mouth disease virus-infected BHK-38 cells Monaghan, Paul; Cook, Hannah; Jackson, Terry Journal of General Virology, Vol. 85, Issue 4 https://doi.org/10.1099/vir.0.19408-0	journal	April 2004
Transcriptional regulation of interferon‐stimulated genes Williams, Bryan R. G. European Journal of Biochemistry, Vol. 200, Issue 1 https://doi.org/10.1111/j.1432-1033.1991.tb21041.x	journal	August 1991
Expanding the Genetic Code of Escherichia coli Wang, L.; Brock, A.; Herberich, B. Science, Vol. 292, Issue 5516, p. 498-500 https://doi.org/10.1126/science.1060077	journal	April 2001
An Expanded Eukaryotic Genetic Code Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher Science, Vol. 301, Issue 5635, p. 964-967 https://doi.org/10.1126/science.1084772	journal	August 2003
Foot-and-Mouth Disease Grubman, M. J.; Baxt, B. Clinical Microbiology Reviews, Vol. 17, Issue 2 https://doi.org/10.1128/CMR.17.2.465-493.2004	journal	April 2004
Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle Medina, Gisselle N.; Montiel, Nestor; Diaz-San Segundo, Fayna Clinical and Vaccine Immunology, Vol. 23, Issue 2 https://doi.org/10.1128/CVI.00426-15	journal	November 2015
A Continuous Bovine Kidney Cell Line Constitutively Expressing Bovine V 6 Integrin Has Increased Susceptibility to Foot-and-Mouth Disease Virus LaRocco, M.; Krug, P. W.; Kramer, E. Journal of Clinical Microbiology, Vol. 51, Issue 6 https://doi.org/10.1128/JCM.03370-12	journal	March 2013
Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo Medina, Gisselle N.; Azzinaro, Paul; Ramirez-Medina, Elizabeth Journal of Virology, Vol. 94, Issue 13 https://doi.org/10.1128/JVI.00341-20	journal	June 2020
Degradation of Nuclear Factor Kappa B during Foot-and-Mouth Disease Virus Infection de los Santos, Teresa; Diaz-San Segundo, Fayna; Grubman, Marvin J. Journal of Virology, Vol. 81, Issue 23 https://doi.org/10.1128/JVI.01467-07	journal	December 2007
Foot-and-Mouth Disease Virus Nonstructural Protein 2C Interacts with Beclin1, Modulating Virus Replication Gladue, D. P.; O'Donnell, V.; Baker-Branstetter, R. Journal of Virology, Vol. 86, Issue 22 https://doi.org/10.1128/JVI.01610-12	journal	August 2012
Interferon-Induced Protection against Foot-and-Mouth Disease Virus Infection Correlates with Enhanced Tissue-Specific Innate Immune Cell Infiltration and Interferon-Stimulated Gene Expression Diaz-San Segundo, Fayna; Moraes, Mauro P.; de los Santos, Teresa Journal of Virology, Vol. 84, Issue 4 https://doi.org/10.1128/JVI.01874-09	journal	February 2010
The Leader Proteinase of Foot-and-Mouth Disease Virus Negatively Regulates the Type I Interferon Pathway by Acting as a Viral Deubiquitinase Wang, Dang; Fang, Liurong; Li, Ping Journal of Virology, Vol. 85, Issue 8 https://doi.org/10.1128/JVI.02589-10	journal	April 2011
Foot-and-Mouth Disease Virus Can Induce a Specific and Rapid CD4+ T-Cell-Independent Neutralizing and Isotype Class-Switched Antibody Response in Naive Cattle Juleff, N.; Windsor, M.; Lefevre, E. A. Journal of Virology, Vol. 83, Issue 8 https://doi.org/10.1128/JVI.02613-08	journal	January 2009
Enhanced Antiviral Activity against Foot-and-Mouth Disease Virus by a Combination of Type I and II Porcine Interferons Moraes, Mauro Pires; de los Santos, Teresa; Koster, Marla Journal of Virology, Vol. 81, Issue 13 https://doi.org/10.1128/JVI.02775-06	journal	July 2007
Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle Pega, J.; Bucafusco, D.; Di Giacomo, S. Journal of Virology, Vol. 87, Issue 5 https://doi.org/10.1128/JVI.02879-12	journal	December 2012
Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus Diaz-San Segundo, Fayna; Dias, Camila C. A.; Moraes, Mauro P. Journal of Virology, Vol. 87, Issue 10 https://doi.org/10.1128/JVI.03462-12	journal	May 2013
Bovine Type III Interferon Significantly Delays and Reduces the Severity of Foot-and-Mouth Disease in Cattle Perez-Martin, Eva; Weiss, Marcelo; Diaz-San Segundo, Fayna Journal of Virology, Vol. 86, Issue 8 https://doi.org/10.1128/JVI.06683-11	journal	February 2012
Ability of Foot-and-Mouth Disease Virus To Form Plaques in Cell Culture Is Associated with Suppression of Alpha/Beta Interferon Chinsangaram, Jarasvech; Piccone, Maria E.; Grubman, Marvin J. Journal of Virology, Vol. 73, Issue 12 https://doi.org/10.1128/JVI.73.12.9891-9898.1999	journal	December 1999
Inhibition of L-Deleted Foot-and-Mouth Disease Virus Replication by Alpha/Beta Interferon Involves Double-Stranded RNA-Dependent Protein Kinase Chinsangaram, Jarasvech; Koster, Marla; Grubman, Marvin J. Journal of Virology, Vol. 75, Issue 12 https://doi.org/10.1128/JVI.75.12.5498-5503.2001	journal	June 2001
Novel Viral Disease Control Strategy: Adenovirus Expressing Alpha Interferon Rapidly Protects Swine from Foot-and-Mouth Disease Chinsangaram, Jarasvech; Moraes, Mauro P.; Koster, Marla Journal of Virology, Vol. 77, Issue 2 https://doi.org/10.1128/JVI.77.2.1621-1625.2003	journal	January 2003
The Leader Proteinase of Foot-and-Mouth Disease Virus Inhibits the Induction of Beta Interferon mRNA and Blocks the Host Innate Immune Response de los Santos, Teresa; de Avila Botton, Sonia; Weiblen, Rudi Journal of Virology, Vol. 80, Issue 4 https://doi.org/10.1128/JVI.80.4.1906-1914.2006	journal	February 2006
BacMam Expressing Highly Glycosylated Porcine Interferon Alpha Induces Robust Antiviral and Adjuvant Effects against Foot-and-Mouth Disease Virus in Pigs Kim, Aro; Lee, Gyeongmin; Hwang, Ji-Hyeon Journal of Virology, Vol. 96, Issue 12 https://doi.org/10.1128/jvi.00528-22	journal	June 2022
Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex Devaney, M. A.; Vakharia, V. N.; Lloyd, R. E. Journal of Virology, Vol. 62, Issue 11 https://doi.org/10.1128/jvi.62.11.4407-4409.1988	journal	November 1988
Interferon-Stimulated Genes: What Do They All Do? Schoggins, John W. Annual Review of Virology, Vol. 6, Issue 1 https://doi.org/10.1146/annurev-virology-092818-015756	journal	September 2019
Immune inhibitory function of bovine CTLA-4 and the effects of its blockade in IFN-γ production Watari, Kei; Konnai, Satoru; Maekawa, Naoya BMC Veterinary Research, Vol. 15, Issue 1 https://doi.org/10.1186/s12917-019-2082-7	journal	October 2019
Immune exhaustion during chronic infections in cattle Konnai, Satoru; Murata, Shiro; Ohashi, Kazuhiko Journal of Veterinary Medical Science, Vol. 79, Issue 1 https://doi.org/10.1292/jvms.16-0354	journal	January 2017
Pathogenesis of Primary Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Vaccinated and Non-Vaccinated Cattle Stenfeldt, Carolina; Eschbaumer, Michael; Pacheco, Juan M. PLOS ONE, Vol. 10, Issue 11 https://doi.org/10.1371/journal.pone.0143666	journal	November 2015
Pegylation: A Novel Process for Modifying Pharmacokinetics Harris, J. Milton; Martin, Nancy E.; Modi, Marlene Clinical Pharmacokinetics, Vol. 40, Issue 7 https://doi.org/10.2165/00003088-200140070-00005	journal	January 2001
Adenovirus serotype 5-vectored foot-and-mouth disease subunit vaccines: the first decade Grubman, Marvin J.; Moraes, Mauro P.; Schutta, Christopher Future Virology, Vol. 5, Issue 1 https://doi.org/10.2217/fvl.09.68	journal	January 2010
Use of a portable real-time reverse transcriptasepolymerase chain reaction assay for rapid detection of foot-and-mouth disease virus Callahan, Johnny D.; Brown, Fred; Osorio, Fernando A. Journal of the American Veterinary Medical Association, Vol. 220, Issue 11 https://doi.org/10.2460/javma.2002.220.1636	journal	June 2002
The Different Tactics of Foot-and-Mouth Disease Virus to Evade Innate Immunity Medina, Gisselle N.; Segundo, Fayna Díaz-San; Stenfeldt, Carolina Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.02644	journal	November 2018
Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV Diaz-San Segundo, Fayna; Medina, Gisselle N.; Azzinaro, Paul Frontiers in Microbiology, Vol. 12 https://doi.org/10.3389/fmicb.2021.668890	journal	May 2021
Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease Medina, Gisselle N.; de los Santos, Teresa; Diaz-San Segundo, Fayna Frontiers in Veterinary Science, Vol. 7 https://doi.org/10.3389/fvets.2020.00465	journal	August 2020
Antiviral Effect of Manganese against Foot-and-Mouth Disease Virus Both in PK15 Cells and Mice Zhang, Zhixiong; Zhang, Rui; Yin, Juanbin Viruses, Vol. 15, Issue 2 https://doi.org/10.3390/v15020390	journal	January 2023
CD4 and CD8 Expression by Dendritic Cell Subtypes in Mouse Thymus and Spleen Vremec, David; Pooley, Joanne; Hochrein, Hubertus The Journal of Immunology, Vol. 164, Issue 6 https://doi.org/10.4049/jimmunol.164.6.2978	journal	March 2000
Cutting Edge: Conventional CD8α+ Dendritic Cells Are Generally Involved in Priming CTL Immunity to Viruses Belz, Gabrielle T.; Smith, Christopher M.; Eichner, Daniel The Journal of Immunology, Vol. 172, Issue 4 https://doi.org/10.4049/jimmunol.172.4.1996	journal	February 2004
Impairment of Thymus-Dependent Responses by Murine Dendritic Cells Infected with Foot-and-Mouth Disease Virus Ostrowski, Matias; Vermeulen, Monica; Zabal, Osvaldo The Journal of Immunology, Vol. 175, Issue 6 https://doi.org/10.4049/jimmunol.175.6.3971	journal	September 2005
IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route Iglesias-Guimarais, Victoria; Ahrends, Tomasz; de Vries, Evert The Journal of Immunology, Vol. 204, Issue 8 https://doi.org/10.4049/jimmunol.1901410	journal	April 2020