{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:59:39Z","timestamp":1777046379077,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Animal and Plant Quarantine Agency of the Ministry of Agriculture, Food, and Rural Affairs of the Republic of Korea","award":["N-1543386-2026-28-01"],"award-info":[{"award-number":["N-1543386-2026-28-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: In the Republic of Korea, a bivalent foot-and-mouth disease (FMD) vaccine covering serotypes O and A is administered to livestock, while antigens for the other serotypes are stockpiled in overseas antigen banks. To achieve self-reliance in FMD vaccine production, various vaccine strains have been developed using in-house technology. Although SAT 3 has historically been confined largely to Africa, preparedness against this serotype remains necessary, as the possibility of its introduction into Korea cannot be completely excluded. Methods: In this regard, we evaluated the commercial potential of the SAT 3 ZIM-R vaccine strain by assessing antigen productivity, scalability, inactivation kinetics, and immunogenicity. Results: Supplementation with 3 mM Ca2+ markedly increased antigen yield compared with that obtained in the absence of calcium. Further optimization showed that antigen yield was highest at pH 8.0\u20138.5. During scale-up, antigen yield was maintained at 9.2\u20139.8 \u03bcg\/mL in flask cultures and remained high at approximately 7.8 \u03bcg\/mL in a bioreactor, demonstrating robust scalability. Treatment with 2 mM binary ethylenimine at 26 \u00b0C achieved complete inactivation within 24 h. Vaccines formulated with the SAT 3 ZIM-R antigen produced either in flasks or in a bioreactor induced comparable neutralizing antibody responses in pigs following both the primary and booster immunizations. Conclusions: Collectively, these findings indicate that SAT 3 ZIM-R is a promising vaccine candidate for large-scale vaccine antigen production and the future establishment of a domestic FMD antigen bank in Korea.<\/jats:p>","DOI":"10.3390\/vaccines14050381","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:28:23Z","timestamp":1777040903000},"page":"381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of an In-House Developed Foot-and-Mouth Disease Virus SAT 3 Vaccine Strain Based on Antigen Productivity and Inactivation Kinetics for Commercial Feasibility"],"prefix":"10.3390","volume":"14","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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"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":"199514","DOI":"10.1016\/j.virusres.2024.199514","article-title":"Foot-and-mouth disease in Asia","volume":"351","author":"Rahman","year":"2025","journal-title":"Virus Res."},{"key":"ref_3","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_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.20506\/rst.26.1.1733","article-title":"Antigen and vaccine banks: Technical requirements and the role of the european antigen bank in emergency foot and mouth disease vaccination","volume":"26","author":"Lombard","year":"2007","journal-title":"Rev. Sci. Tech."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1016\/S0264-410X(00)00399-6","article-title":"The suitability of the \u2018emergency\u2019foot-and-mouth disease antigens held by the International Vaccine Bank within a global context","volume":"19","author":"Barnett","year":"2001","journal-title":"Vaccine"},{"key":"ref_8","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_9","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_10","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":"Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol."},{"key":"ref_11","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_12","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_13","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_14","doi-asserted-by":"crossref","unstructured":"Kim, A.Y., Park, S.Y., Park, S.H., Kim, J.Y., Jin, J.S., Kim, E.S., Park, J.H., and Ko, Y.J. (2022). Comparison of high-performance liquid chromatography with sucrose density gradient ultracentrifugation for the quantification of foot-and-mouth disease vaccine antigens. Vaccines, 10.","DOI":"10.3390\/vaccines10050667"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e02431","DOI":"10.1128\/JVI.02431-20","article-title":"A possible action of divalent transition metal ions at the interpentameric 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_16","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."},{"key":"ref_17","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_18","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_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.virusres.2019.02.012","article-title":"Inherent biophysical stability of foot-and-mouth disease SAT1, SAT2 and SAT3 viruses","volume":"264","author":"Scott","year":"2019","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1099\/jgv.0.000462","article-title":"Application of the thermofluor PaSTRy technique for improving foot-and-mouth disease virus vaccine formulation","volume":"97","author":"Kotecha","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jviromet.2012.06.014","article-title":"A plate-based high-throughput assay for virus stability and vaccine formulation","volume":"185","author":"Walter","year":"2012","journal-title":"J. Virol. Methods"},{"key":"ref_22","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."},{"key":"ref_23","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. New York Acad. Sci."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/BF01242879","article-title":"A simple method for the quantification of 140 S particles of foot-and-mouth disease virus (FMDV)","volume":"45","author":"Barteling","year":"1974","journal-title":"Arch. Gesamte Virusforsch."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"114379","DOI":"10.1016\/j.jviromet.2021.114379","article-title":"Effect of cell density on the biological titer and yield of 146S fraction of foot-and-mouth disease virus O in cell suspension","volume":"300","author":"Rizvi","year":"2022","journal-title":"J. Virol. Methods"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Park, S.Y., Jin, J.S., Kim, D., Park, J.-H., Park, S.H., and Ko, Y.-J. (2023). Efficacy of binary ethylenimine in the inactivation of foot-and-mouth disease virus for vaccine production in South Korea. Pathogens, 12.","DOI":"10.3390\/pathogens12060760"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF01320790","article-title":"Thermal stability of foot-and-mouth disease virus","volume":"70","author":"Doel","year":"1981","journal-title":"Arch. Virol."},{"key":"ref_31","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"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kim, J., Lee, S.H., Kim, H.H., Shin, S.H., Park, S.H., Park, J.H., and Park, C.K. (2023). An alternative serological measure for as-sessing foot-and-mouth disease vaccine efficacy against homologous and heterologous viral challenges in pigs. Vaccines, 12.","DOI":"10.3390\/vaccines12010010"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/5\/381\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:42:20Z","timestamp":1777041740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/5\/381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["vaccines14050381"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14050381","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]}}}