{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T11:00:33Z","timestamp":1764241233661,"version":"3.46.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"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":"publisher","award":["B-1543386-2025-27-03"],"award-info":[{"award-number":["B-1543386-2025-27-03"]}],"id":[{"id":"10.13039\/501100008771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals such as cattle and pigs, characterized by vesicular lesions in the mouth, nose, teats, and feet. Globally, the most commonly used FMD vaccines are inactivated vaccines produced by chemical inactivation of the infectious FMD virus (FMDV). This study aimed to establish an infectious clone of the O\/Boeun\/SKR\/2017 virus that has demonstrated the highest antigen productivity among the various type O vaccine strains developed in South Korea to date. Methods: An infectious clone was generated from a type O virus isolated during the 2017 FMD outbreak in South Korea. The viral genome was divided into two fragments, each amplified separately, and subsequently ligated to produce a full-length infectious clone. Results: Rescue of infectious FMDV was confirmed using a commercial antigen detection kit and electron microscopy. Under optimized culture conditions, the rescued virus titer reached 2 \u00d7 107 TCID50\/mL, and the antigen yield was 6.4 \u00b5g\/mL. Following inactivation, the antigen was formulated into a vaccine and administered to pigs. Four weeks post-vaccination, challenge with the live virus resulted in no clinical symptoms, demonstrating complete protective efficacy. Conclusions: To the best of our knowledge, this is the first report describing the construction of an infectious clone derived from a field FMDV isolate in South Korea and its application in vaccine development. The O\/Boeun\/SKR\/2017 infectious clone may serve as a genetic backbone for the rapid generation of new FMD vaccine candidates with high antigen productivity by substituting epitopes from other FMDV.<\/jats:p>","DOI":"10.3390\/vaccines13121195","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:56:41Z","timestamp":1764172601000},"page":"1195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction of a Full-Length Infectious Clone Derived from Type O Foot-and-Mouth Disease Virus Isolated in South Korea for Vaccine Development with High Antigen Productivity"],"prefix":"10.3390","volume":"13","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":[{"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, Gyeongsangbuk-do, 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, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Hyun","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Sook","family":"Jin","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":[{"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, Gyeongsangbuk-do, 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, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1865-1682.2011.01236.x","article-title":"The pathogenesis of foot-and-mouth disease II: Viral pathways in swine, small ruminants, and wildlife; myotropism, chronic syndromes, and molecular virus\u2013host interactions","volume":"58","author":"Arzt","year":"2011","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.coviro.2017.11.013","article-title":"Understanding the transmission of foot-and-mouth disease virus at different scales","volume":"28","author":"Paton","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s00253-019-10280-9","article-title":"Engineering viable foot-and-mouth disease viruses with increased acid stability facilitate the development of improved vaccines","volume":"104","author":"Yuan","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1099\/jgv.0.000306","article-title":"Employing transposon mutagenesis to investigate foot-and-mouth disease virus replication","volume":"96","author":"Herod","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0168-1702(02)00261-7","article-title":"FMD vaccines","volume":"91","author":"Doel","year":"2003","journal-title":"Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2025.2454482","article-title":"Global foot-and-mouth disease risk assessment based on multiple spatial analysis and ecological niche model","volume":"45","author":"An","year":"2025","journal-title":"Vet. Q."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"199140","DOI":"10.1016\/j.virusres.2023.199140","article-title":"Emergence of a novel genetic lineage \u2018A\/ASIA\/G-18\/2019\u2032 of foot and mouth disease virus serotype A in India: A challenge to reckon with","volume":"333","author":"Mohapatra","year":"2023","journal-title":"Virus Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1016\/j.vaccine.2014.08.033","article-title":"Genetic and antigenic characterisation of serotype A FMD viruses from East Africa to select new vaccine strains","volume":"32","author":"Bari","year":"2014","journal-title":"Vaccine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2024.2367215","article-title":"Complete coding region sequence analyses and antigenic characterization of emerging lineage G-IX of foot-and-mouth disease virus serotype Asia1","volume":"44","author":"Rout","year":"2024","journal-title":"Vet. Q."},{"key":"ref_10","first-page":"368","article-title":"Eastern Africa Origin of SAT2 Topotype XIV Foot-and-Mouth Disease Virus Outbreaks, Western Asia, 2023","volume":"31","author":"Shaw","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Park, M.-Y., Han, Y.J., Choi, E.-J., Kim, H., Pervin, R., Shin, W., Kwon, D., Kim, J.M., and Pyo, H.M. (2021). Post-vaccination monitoring to assess foot-and-mouth disease immunity at population level in Korea. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.673820"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Habtewold, W.T., Welde, N., Kenubih, A., Getahun, Y.A., Abayneh, T., Getachew, B., Woldemedhin, W., Tesfaye, Y., Tesfaw, L., and Getachew, Y. (2025). Effects of binary ethyleneimine and formaldehyde inactivation methods on foot-and-mouth disease virus vaccine immune responses and kinetics. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-01292-9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12038-009-0008-4","article-title":"Construction of an infectious cDNA clone of foot-and-mouth disease virus type O1BFS 1860 and its use in the preparation of candidate vaccine","volume":"34","author":"Hema","year":"2009","journal-title":"J. Biosci."},{"key":"ref_14","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_15","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_16","doi-asserted-by":"crossref","unstructured":"Kim, A.-Y., Park, S.Y., Park, S.H., Jin, J.S., Kim, E.-S., Kim, J.Y., Park, J.-H., and Ko, Y.-J. (2021). Validation of pretreatment methods for the in-process quantification of foot-and-mouth disease vaccine antigens. Vaccines, 9.","DOI":"10.3390\/vaccines9111361"},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1128\/CVI.00018-09","article-title":"Innate immune defenses induced by CpG do not promote vaccine-induced protection against foot-and-mouth disease virus in pigs","volume":"16","author":"Alves","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_19","unstructured":"WOAH (2022). WOAH Terrestrial Manual 2022. Foot and Mouth Disease (Infection with Foot and Motu Disease Virus), WOAH."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zheng, H., Guo, J., Jin, Y., Yang, F., He, J., Lv, L., Zhang, K., Wu, Q., Liu, X., and Cai, X. (2013). Engineering foot-and-mouth disease viruses with improved growth properties for vaccine development. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055228"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.rvsc.2016.03.017","article-title":"Construction and characterization of a full-length infectious cDNA clone of foot-and-mouth disease virus strain O\/JPN\/2010 isolated in Japan in 2010","volume":"106","author":"Nishi","year":"2016","journal-title":"Res. Vet. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.virusres.2015.06.008","article-title":"Recovery of infectious type Asia1 foot-and-mouth disease virus from suckling mice directly inoculated with an RNA polymerase I\/II-driven unidirectional transcription plasmid","volume":"208","author":"Lian","year":"2015","journal-title":"Virus Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Semkum, P., Thangthamniyom, N., Chankeeree, P., Keawborisuth, C., Theerawatanasirikul, S., and Lekcharoensuk, P. (2023). The application of the Gibson assembly method in the production of two pKLS3 vector-derived infectious clones of foot-and-mouth disease virus. Vaccines, 11.","DOI":"10.3390\/vaccines11061111"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/abbs\/gmp093","article-title":"Recovery of infectious foot-and-mouth disease virus from full-length genomic cDNA clones using an RNA polymerase I system","volume":"41","author":"Chang","year":"2009","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1128\/jvi.64.6.2467-2473.1990","article-title":"Infectious foot-and-mouth disease virus derived from a cloned full-length cDNA","volume":"64","author":"Zibert","year":"1990","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1099\/vir.0.19509-0","article-title":"Studies of genetically defined chimeras of a European type A virus and a South African Territories type 2 virus reveal growth determinants for foot-and-mouth disease virus","volume":"85","author":"Henry","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.7774\/cevr.2015.4.1.114","article-title":"Antigenic properties and virulence of foot-and-mouth disease virus rescued from full-length cDNA clone of serotype O, typical vaccine strain","volume":"4","author":"Kim","year":"2015","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/nsmb.3096","article-title":"Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design","volume":"22","author":"Kotecha","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_29","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_30","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_31","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_32","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_33","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_34","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_35","doi-asserted-by":"crossref","unstructured":"Dill, V., Zimmer, A., Beer, M., and Eschbaumer, M. (2020). Targeted modification of the foot-and-mouth disease virus genome for quick cell culture adaptation. Vaccines, 8.","DOI":"10.20944\/preprints202008.0712.v1"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Park, S.-H., Lee, S.-Y., Kim, J.-S., Kim, A.-Y., Park, S.-Y., Lee, J.-H., Lee, M., Kim, H., Lee, S.-I., and Kang, N.-Y. (2021). Scale-up production of type O and a foot-and-mouth disease bivalent vaccine and its protective efficacy in pigs. Vaccines, 9.","DOI":"10.3390\/vaccines9060586"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11262-019-01714-7","article-title":"Cell culture propagation of foot-and-mouth disease virus: Adaptive amino acid substitutions in structural proteins and their functional implications","volume":"56","author":"Dill","year":"2020","journal-title":"Virus Genes"},{"key":"ref_38","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. (2024). An alternative serological measure for assessing foot-and-mouth disease vaccine efficacy against homologous and heterologous viral challenges in pigs. Vaccines, 12.","DOI":"10.3390\/vaccines12010010"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hwang, J.-h., Lee, K.-N., Kim, S.-M., Kim, H., Park, S.-H., Kim, D.-W., Cho, G., Lee, Y.-H., Lee, J.-S., and Park, J.-H. (2024). Enhanced Effects of ISA 207 Adjuvant via Intradermal Route in Foot-and-Mouth Disease Vaccine for Pigs. Vaccines, 12.","DOI":"10.3390\/vaccines12090963"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104920","DOI":"10.1016\/j.antiviral.2020.104920","article-title":"Vaccine strain of O\/ME-SA\/Ind-2001e of foot-and-mouth disease virus provides high immunogenicity and broad antigenic coverage","volume":"182","author":"Lee","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1099\/vir.0.043521-0","article-title":"Characterization of epitope-tagged foot-and-mouth disease virus","volume":"93","author":"Seago","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.biologicals.2015.06.001","article-title":"Engineering foot-and-mouth disease virus serotype O IND R2\/1975 for one-step purification by immobilized metal affinity chromatography","volume":"43","author":"Biswal","year":"2015","journal-title":"Biologicals"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Childs, K., Juleff, N., Moffat, K., and Seago, J. (2021). Demonstration of Co-Infection and Trans-Encapsidation of Viral RNA In Vitro Using Epitope-Tagged Foot-and-Mouth Disease Viruses. Viruses, 13.","DOI":"10.3390\/v13122433"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jviromet.2016.09.013","article-title":"Construction of stabilized and tagged foot-and-mouth disease virus","volume":"237","author":"Park","year":"2016","journal-title":"J. Virol. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.virol.2016.04.027","article-title":"Novel 6xHis tagged foot-and-mouth disease virus vaccine bound to nanolipoprotein adjuvant via metal ions provides antigenic distinction and effective protective immunity","volume":"495","author":"Rai","year":"2016","journal-title":"Virology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jviromet.2007.01.025","article-title":"Development of an epitope-blocking-enzyme-linked immunosorbent assay to differentiate between animals infected with and vaccinated against foot-and-mouth disease virus","volume":"142","author":"Oem","year":"2007","journal-title":"J. Virol. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Fu, Y., Lu, Z., Li, P., Cao, Y., Sun, P., Tian, M., Wang, N., Bao, H., Bai, X., and Li, D. (2014). Development of a blocking ELISA based on a monoclonal antibody against a predominant epitope in non-structural protein 3B2 of foot-and-mouth disease virus for differentiating infected from vaccinated animals. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111737"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Choi, J.-H., Ko, M.-K., Shin, S.H., You, S.-H., Jo, H.-E., Jo, H., Lee, M.J., Kim, S.-M., Lee, J.-S., and Kim, B. (2019). Improved foot-and-mouth disease vaccine, O TWN-R, protects pigs against SEA topotype virus occurred in South Korea. Vet. Microbiol., 236.","DOI":"10.1016\/j.vetmic.2019.07.026"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.vetmic.2019.05.016","article-title":"Evaluation of novel inactivated vaccine for type C foot-and-mouth disease in cattle and pigs","volume":"234","author":"You","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"e02312-16","DOI":"10.1128\/JVI.02312-16","article-title":"SAT2 foot-and-mouth disease virus structurally modified for increased thermostability","volume":"91","author":"Scott","year":"2017","journal-title":"J. Virol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/12\/1195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:57:36Z","timestamp":1764241056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/12\/1195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["vaccines13121195"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13121195","relation":{},"ISSN":["2076-393X"],"issn-type":[{"type":"electronic","value":"2076-393X"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}