{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:12Z","timestamp":1785434832398,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008771","name":"Animal and Plant Quarantine Agency","doi-asserted-by":"crossref","award":["N-1543386-2026-28-01"],"award-info":[{"award-number":["N-1543386-2026-28-01"]}],"id":[{"id":"10.13039\/501100008771","id-type":"DOI","asserted-by":"crossref"}]},{"award":["N-1543386-2026-28-01"],"award-info":[{"award-number":["N-1543386-2026-28-01"]}],"id":[{"id":"https:\/\/ror.org\/04sbe6g90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Republic of Korea has implemented routine vaccination against foot-and-mouth disease virus (FMDV) in livestock using a bivalent vaccine comprising serotypes O and A following the massive FMD outbreak in 2010, while antigens for the remaining serotypes are maintained in overseas antigen banks. The recent geographic expansion of FMDV Southern African Territories 1 (SAT1) beyond Africa underscores the need for enhanced preparedness in previously unaffected regions. In this study, we evaluated the SAT1 BOT-R strain as a candidate vaccine seed for potential domestic vaccine production by optimizing antigen production conditions, assessing scalability, determining virus inactivation parameters, and examining immunogenicity in pigs. Optimal antigen yield was achieved at 20 h\u221224 h post infection with a multiplicity of infection of 0.005\u22120.01, with production remaining stable under mildly alkaline conditions. Antigen productivity was consistently maintained during scale-up from shake flasks to a bioreactor, yielding up to 9.5 \u03bcg\/mL. Complete virus inactivation was achieved using binary ethylenimine at 2 mM for 24 h at 26 \u00b0C. Vaccines formulated from both flask- and bioreactor-derived antigens elicited comparable neutralizing antibody responses in pigs, reaching a median titer of 1:500 following booster immunization. Collectively, these findings demonstrate that the SAT1 BOT-R strain is a viable and scalable candidate for SAT1 antigen banking and future domestic vaccine production, providing a practical framework for strengthening national preparedness against potential incursions of FMDV SAT1.<\/jats:p>","DOI":"10.3390\/v18050537","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:39:47Z","timestamp":1778150387000},"page":"537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Antigen Productivity and Inactivation Kinetics of a Recombinant Foot-and-Mouth Disease SAT1 Vaccine Strain"],"prefix":"10.3390","volume":"18","author":[{"given":"Jae Young","family":"Kim","sequence":"first","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2784-513X","authenticated-orcid":false,"given":"Sun Young","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeongmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-A","family":"Hwangbo","sequence":"additional","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giyoun","family":"Cho","sequence":"additional","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-8121","authenticated-orcid":false,"given":"Jong-Hyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-8175","authenticated-orcid":false,"given":"Young-Joon","family":"Ko","sequence":"additional","affiliation":[{"name":"Center for Foot-and-Mouth Disease Vaccine Research, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13567-025-01561-5","article-title":"Epidemiology and economics of foot-and-mouth disease: Current understanding and knowledge gaps","volume":"56","author":"Humphreys","year":"2025","journal-title":"Vet. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/1467-8489.12546","article-title":"The economic impacts of a hypothetical foot and mouth disease outbreak in Australia","volume":"68","author":"Wittwer","year":"2024","journal-title":"Aust. J. Agric. Resour. Econ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12985-016-0561-z","article-title":"Biological function of foot-and-mouth disease virus non-structural proteins and non-coding elements","volume":"13","author":"Gao","year":"2016","journal-title":"Virol. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/j.1460-2075.1983.tb01462.x","article-title":"The molecular basis of the antigenic variation of foot-and-mouth disease virus","volume":"2","author":"Beck","year":"1983","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1038\/s41467-024-53165-w","article-title":"Generative learning for forecasting the dynamics of high-dimensional complex systems","volume":"15","author":"Gao","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11275","DOI":"10.1128\/JVI.01263-09","article-title":"Foot-and-mouth disease virus assembly: Processing of recombinant capsid precursor by exogenous protease induces self-assembly of pentamers in vitro in a myristoylation-dependent manner","volume":"83","author":"Goodwin","year":"2009","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Malik, N., Kotecha, A., Gold, S., Asfor, A., Ren, J., Huiskonen, J.T., Tuthill, T.J., Fry, E.E., and Stuart, D.I. (2017). Structures of foot-and-mouth disease virus pentamers: Insight into capsid dissociation and unexpected pentamer reassociation. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006607"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8774","DOI":"10.1038\/s41467-024-53027-5","article-title":"Foot-and-mouth disease virus antigenic landscape and reduced immunogenicity elucidated in atomic detail","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Li, Y., Yang, R., Yin, F., Zhang, H., Zhai, G., Sun, S., Tian, B., and Zeng, Q. (2024). Correlation between 146S antigen content in foot-and-mouth disease inactivated vaccines and immunogenicity level and vaccine potency alternative test methods. Vet. Sci., 11.","DOI":"10.3390\/vetsci11040168"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/BF01314726","article-title":"Comparative immunogenicity of 146S, 75S and 12S particles of foot-and-mouth disease virus","volume":"73","author":"Doel","year":"1982","journal-title":"Arch. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.vaccine.2004.08.034","article-title":"Protection against direct-contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx","volume":"23","author":"Cox","year":"2005","journal-title":"Vaccine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.vetmic.2016.12.018","article-title":"Foot-and-mouth disease vaccines","volume":"206","author":"Medina","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Aslam, M., and Alkheraije, K.A. (2023). The prevalence of foot-and-mouth disease in Asia: A systematic review and meta-analysis. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1201578"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12985-019-1262-1","article-title":"Evaluation of novel inactivated vaccines for the SAT 1, SAT 2 and SAT 3 serotypes of foot-and-mouth disease in pigs","volume":"16","author":"Jo","year":"2019","journal-title":"Virol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/BF01863914","article-title":"Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche","volume":"162","year":"1931","journal-title":"Arch. Exp. Pathol. Pharmakol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.1016\/j.vaccine.2019.07.051","article-title":"Validation of a high performance liquid chromatography method for quantitation of foot-and-mouth disease virus antigen in vaccines and vaccine manufacturing","volume":"37","author":"Spitteler","year":"2019","journal-title":"Vaccine"},{"key":"ref_17","unstructured":"World Organisation for Animal Health (2022). Chapter 3.1.8. Foot and Mouth Disease (Infection with Foot and Mouth Disease Virus). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, World Organisation for Animal Health. Available online: https:\/\/www.woah.org\/en\/what-we-do\/standards\/codes-and-manuals\/terrestrial-manual-online-access\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/s13567-025-01643-4","article-title":"Evolutionary and structural insights into VP1 epitopes of representative SAT-type FMDV strains: Implications for candidate vaccine selection","volume":"56","author":"Jiang","year":"2025","journal-title":"Vet. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alkhamis, M.A., Abouelhassan, H., Alateeqi, A., Husain, A., Humphreys, J.M., Arzt, J., and Perez, A.M. (2025). Predicting the landscape epidemiology of foot-and-mouth disease in endemic regions: An interpretable machine learning approach. Viruses, 17.","DOI":"10.3390\/v17101383"},{"key":"ref_20","unstructured":"Department for Environment, and Food and Rural Affairs (DEFRA) (2026, April 27). Updated Outbreak Assessment #3: Foot and Mouth Disease in Cyprus and Greece, 17 April 2026, Available online: https:\/\/www.gov.uk\/government\/collections\/animal-diseases-international-monitoring."},{"key":"ref_21","unstructured":"Food and Agriculture Organization of the United Nations (FAO) (2026). FAO Alerts Countries in Asia and the Pacific to Enhance Preparedness for Foot-and-Mouth Disease SAT1, FAO. Available online: https:\/\/www.fao.org\/animal-health."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/BF01242879","article-title":"A simple method for the quantification of 140S particles of foot-and-mouth disease virus (FMDV)","volume":"45","author":"Barteling","year":"1974","journal-title":"Arch. Gesamte Virusforsch."},{"key":"ref_23","first-page":"209","article-title":"Further developments in the quantification of small RNA viruses by UV photometry of sucrose density gradients","volume":"50","author":"Doel","year":"1981","journal-title":"Dev. Biol. Stand."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.vaccine.2015.01.031","article-title":"Size-exclusion HPLC provides a simple, rapid, and versatile alternative method for quality control of vaccines by characterizing the assembly of antigens","volume":"33","author":"Yang","year":"2015","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kim, D., Park, S.Y., Lee, G., Kim, E.-S., Jin, J.-S., Kim, J.Y., Lee, S., Park, J.-H., and Ko, Y.-J. (2024). Calcium chloride treatment enhances antigen production in foot-and-mouth disease vaccines for serotypes SAT1 and SAT3. Vaccines, 12.","DOI":"10.3390\/vaccines12030231"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e02431-20","DOI":"10.1128\/JVI.02431-20","article-title":"A possible action of divalent transition metal ions at the inter-pentameric interface of inactivated foot-and-mouth disease virus provides a simple but effective approach to enhance stability","volume":"95","author":"Lin","year":"2021","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"463301","DOI":"10.1016\/j.chroma.2022.463301","article-title":"Size exclusion chromatography using large pore size media induces adverse conformational changes of inactivated foot-and-mouth disease virus particles","volume":"1677","author":"Song","year":"2022","journal-title":"J. Chromatogr. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1007\/s007050050233","article-title":"Early interactions of hepatitis A virus with cultured cells: Viral elution and the effect of pH and calcium ions","volume":"142","author":"Bishop","year":"1997","journal-title":"Arch. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Park, S.Y., Lee, G., Kwon, M., Jin, J.S., Park, J.-H., and Ko, Y.-J. (2025). Evaluation of recombinant foot-and-mouth disease SAT2 vaccine strain in terms of antigen productivity, virus inactivation kinetics, and immunogenicity in pigs for domestic antigen bank. Vaccines, 13.","DOI":"10.3390\/vaccines13070704"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"747","DOI":"10.20506\/rst.8.3.425","article-title":"Effect of formaldehyde and binary ethyleneimine (BEI) on the integrity of foot-and-mouth disease virus capsid","volume":"8","author":"Rweyemamu","year":"1989","journal-title":"Rev. Sci. Tech. Off. Int. Epiz."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1749-6632.2002.tb04355.x","article-title":"Construction and evaluation of a recombinant foot-and-mouth disease virus: Implications for inactivated vaccine production","volume":"969","author":"Mason","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.biologicals.2004.09.001","article-title":"Validation of binary ethyleneimine (BEI) used as an inactivant for foot and mouth disease tissue culture vaccine","volume":"32","author":"Aarthi","year":"2004","journal-title":"Biologicals"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6380","DOI":"10.1016\/j.vaccine.2019.09.013","article-title":"A scale-down model of 4000-L cell culture process for inactivated foot-and-mouth disease vaccine production","volume":"37","author":"Li","year":"2019","journal-title":"Vaccine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1002\/btpr.2134","article-title":"Application of multivariate analysis and mass transfer principles for refinement of a 3-L bioreactor scale-down model\u2014When shake flasks mimic 15,000-L bioreactors better","volume":"31","author":"Ahuja","year":"2015","journal-title":"Biotechnol. Prog."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00253-010-2742-9","article-title":"MDCK and Vero cells for influenza virus vaccine production: A one-to-one comparison up to lab-scale bioreactor cultivation","volume":"88","author":"Genzel","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gubbins, S., Paton, D.J., Dekker, A., Ludi, A.B., Wilsden, G., Browning, C.F., Eschbaumer, M., Barnabei, J., Duque, H., and Pauszek, L.L. (2022). Predicting cross-protection against foot-and-mouth disease virus strains by serology after vaccination. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.1027006"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/5\/537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:39:59Z","timestamp":1778215199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/5\/537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["v18050537"],"URL":"https:\/\/doi.org\/10.3390\/v18050537","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}