{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:25:16Z","timestamp":1790486716141,"version":"4.1.0"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Foot-and-mouth disease virus (FMDV) is one of the most significant animal pathogens worldwide, severely impacting the health and productivity of pigs, cattle, sheep, and other ungulates. Although the traditional vaccines have played a crucial role in epidemic control, inactivated vaccines face persistent challenges concerning the potential for virus dissemination and pressures from serotype and subtype matching. However, the manufacture of attenuated vaccines is forbidden, and the efficiency of alternative vaccines for immune protection is still inadequate. Consequently, there exists an urgent need for safer and more effective innovative vaccines in animal husbandry. In this study, we aimed to develop a lipid nanoparticle mRNA vaccine based on VP1-3A-3D epitopes from serotype O FMD and to verify its specific expression within cytoplasmic and injection sites. Our findings demonstrated that mRNA transfected into primary spleen cells derived from guinea pigs induced cytokine release, promoted differentiation of both CD4<jats:sup>+<\/jats:sup> T and CD8<jats:sup>+<\/jats:sup> T lymphocytes, and enhanced lymphocyte proliferation rates. Following immunization of mRNA vaccine in guinea pigs, we observed increased differentiation of both CD4<jats:sup>+<\/jats:sup> T and CD8<jats:sup>+<\/jats:sup> T cells, alongside elevated levels of cytokine secretion. Additionally, this vaccination induced the production of specific IgG antibodies as well as neutralizing antibodies. Importantly, our vaccine provided complete protection for all six guinea pigs against a lethal challenge of 100 GPID<jats:sub>50<\/jats:sub>, with histopathological scores indicating protection equivalent to that conferred by the inactivated vaccine. The viral load results demonstrated that the vaccine group significantly reduced viral copy numbers in serum and effectively decreased the concentration of the inflammatory cytokine IL-1\u03b2. Furthermore, during the pre-immune phase following vaccination with the mRNA vaccine in pigs, heightened cytokine secretion was observed, along with the inhibition of viral replication. Simultaneously, the neutralizing antibody titer in the serum remained stable over 4 months. Immunofluorescence analysis of spleen tissues from both guinea pigs and pigs demonstrated marked activation and increased expression of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T lymphocytes, as well as macrophages, in the mRNA vaccine group. In summary, this study suggests that the serotype O FMD mRNA vaccine is a promising candidate for further development in the fight against FMDV.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1503191","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T12:02:48Z","timestamp":1745841768000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine"],"prefix":"10.3389","volume":"16","author":[{"given":"Jingang","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiguo","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heran","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/vaccines12020134","article-title":"Advances in poultry vaccines: leveraging biotechnology for improving vaccine development, stability, and delivery","volume":"12","author":"Abdelaziz","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"103458","DOI":"10.1016\/j.drudis.2022.103458","article-title":"Current state of, prospects for, and obstacles to mRNA vaccine development","volume":"28","author":"Aljabali","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref3","doi-asserted-by":"publisher","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":"ref4","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1126\/science.abm0271","article-title":"A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes","volume":"378","author":"Arevalo","year":"2022","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"7469","DOI":"10.1038\/s41467-024-50376-z","article-title":"Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases","volume":"15","author":"Baden","year":"2024","journal-title":"Nat. Commun."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/s41587-022-01294-2","article-title":"The clinical progress of mRNA vaccines and immunotherapies","volume":"40","author":"Barbier","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"396","DOI":"10.3389\/fvets.2020.00396","article-title":"A new cage-like particle adjuvant enhances protection of foot-and-mouth disease vaccine","volume":"7","author":"Bidart","year":"2020","journal-title":"Front. Vet. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1586\/14760584.2014.963562","article-title":"Adjuvants for foot-and-mouth disease virus vaccines: recent progress","volume":"13","author":"Cao","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1099\/vir.0.045732-0","article-title":"CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle","volume":"94","author":"Carr","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.3390\/vaccines10122181","article-title":"Efficacy of a novel multiepitope vaccine candidate against foot-and-mouth disease virus serotype O and a","volume":"10","author":"Chathuranga","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","article-title":"mRNA vaccines for infectious diseases: principles, delivery and clinical translation","volume":"20","author":"Chaudhary","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3390\/v14010022","article-title":"FMDV leader protein interacts with the NACHT and LRR domains of NLRP3 to promote IL-1\u03b2 production","volume":"14","author":"Choudhury","year":"2021","journal-title":"Viruses"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev-immunol-093019-111748","article-title":"Origins, biology, and diseases of tissue macrophages","volume":"39","author":"Cox","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.xphs.2020.12.006","article-title":"Addressing the cold reality of mRNA vaccine stability","volume":"110","author":"Crommelin","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"7223","DOI":"10.1128\/jvi.00401-08","article-title":"Enhanced mucosal immunoglobulin a response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide","volume":"82","author":"Cubillos","year":"2008","journal-title":"J. Virol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.coviro.2018.02.005","article-title":"The need for improved vaccines against foot-and-mouth disease","volume":"29","author":"de Los Santos","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3390\/vaccines8030406","article-title":"Designing functionally versatile, highly immunogenic peptide-based Multiepitopic vaccines against foot-and-mouth disease virus","volume":"8","author":"Defaus","year":"2020","journal-title":"Vaccines (Basel)"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1126\/science.3008333","article-title":"Protection of cattle against foot-and-mouth disease by a synthetic peptide","volume":"232","author":"DiMarchi","year":"1986","journal-title":"Science"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3435","DOI":"10.1016\/j.vaccine.2019.05.019","article-title":"The VP1 G-H loop hypervariable epitope contributes to protective immunity against foot and mouth disease virus in swine","volume":"37","author":"Fernandez-Sainz","year":"2019","journal-title":"Vaccine"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3390\/vaccines9050477","article-title":"Peptide-based vaccines: foot-and-mouth disease virus, a paradigm in animal health","volume":"9","author":"Forner","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1101\/2023.04.30.538854","article-title":"Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus","author":"Furey","year":"2023","journal-title":"bioRxiv"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"abm0829","DOI":"10.1126\/science.abm0829","article-title":"mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern","volume":"374","author":"Goel","year":"2021","journal-title":"Science"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.3390\/ijms24032700","article-title":"A comprehensive review of mRNA vaccines","volume":"24","author":"Gote","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1128\/cmr.17.2.465-493.2004","article-title":"Foot-and-mouth disease","volume":"17","author":"Grubman","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1027006","DOI":"10.3389\/fvets.2022.1027006","article-title":"Predicting cross-protection against foot-and-mouth disease virus strains by serology after vaccination","volume":"9","author":"Gubbins","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"12375","DOI":"10.1128\/jvi.01545-10","article-title":"Induction of a cross-reactive CD8(+) T cell response following foot-and-mouth disease virus vaccination","volume":"84","author":"Guzman","year":"2010","journal-title":"J. Virol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"554305","DOI":"10.3389\/fvets.2020.554305","article-title":"Novel foot-and-mouth disease vaccine platform: formulations for safe and DIVA-compatible FMD vaccines with improved potency","volume":"7","author":"Hardham","year":"2020","journal-title":"Front. Vet. Sci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1080\/17425247.2019.1669558","article-title":"Lipid-based nanoparticle formulations for small molecules and RNA drugs","volume":"16","author":"Ickenstein","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"L967","DOI":"10.1152\/ajplung.00144.2011","article-title":"Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action","volume":"303","author":"Ionescu","year":"2012","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/1297-9716-44-116","article-title":"Foot-and-mouth disease: past, present and future","volume":"44","author":"Jamal","year":"2013","journal-title":"Vet. Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41541-021-00304-9","article-title":"The HSP70-fused foot-and-mouth disease epitope elicits cellular and humoral immunity and drives broad-spectrum protective efficacy","volume":"6","author":"Jo","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.vetmic.2009.05.004","article-title":"Calcium phosphate nanoparticle prepared with foot and mouth disease virus P1-3CD gene construct protects mice and guinea pigs against the challenge virus","volume":"139","author":"Joyappa","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1007\/s00705-019-04216-x","article-title":"Foot-and-mouth disease vaccines: recent updates and future perspectives","volume":"164","author":"Kamel","year":"2019","journal-title":"Arch. Virol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"114961","DOI":"10.1016\/j.addr.2023.114961","article-title":"Advancements of in vitro transcribed mRNA (IVT mRNA) to enable translation into the clinics","volume":"199","author":"Kang","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41541-022-00455-3","article-title":"Calibrated comparison of SARS-CoV-2 neutralizing antibody levels in response to protein-, mRNA-, and vector-based COVID-19 vaccines","volume":"7","author":"Karbiener","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1038\/mt.2008.200","article-title":"Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability","volume":"16","author":"Karik\u00f3","year":"2008","journal-title":"Mol. Ther."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"205","DOI":"10.2147\/vmrr.S319761","article-title":"Foot and mouth disease vaccine development and challenges in inducing Long-lasting immunity: trends and current perspectives","volume":"12","author":"Kenubih","year":"2021","journal-title":"Vet. Med. (Auckl.)"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13273-021-00171-4","article-title":"Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency","volume":"18","author":"Kim","year":"2022","journal-title":"Mol. Cell. Toxicol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.meegid.2008.11.005","article-title":"Understanding the molecular epidemiology of foot-and-mouth-disease virus","volume":"9","author":"Klein","year":"2009","journal-title":"Infect. Genet. Evol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.prevetmed.2013.07.013","article-title":"The economic impacts of foot and mouth disease - what are they, how big are they and where do they occur?","volume":"112","author":"Knight-Jones","year":"2013","journal-title":"Prev. Vet. Med."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41590-022-01168-4","article-title":"Making innate sense of mRNA vaccine adjuvanticity","volume":"23","author":"Kobiyama","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.imlet.2017.07.007","article-title":"Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis","volume":"190","author":"Kou","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1161\/01.cir.90.3.1398","article-title":"Effects of reperfusion on ischemic right ventricular dysfunction. Disparate mechanisms of benefit related to duration of ischemia","volume":"90","author":"Laster","year":"1994","journal-title":"Circulation"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41586-023-06002-x","article-title":"Physiology and diseases of tissue-resident macrophages","volume":"618","author":"Lazarov","year":"2023","journal-title":"Nature"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1147652","DOI":"10.3389\/fmicb.2023.1147652","article-title":"Molecular evolution, diversity, and adaptation of foot-and-mouth disease virus serotype O in Asia","volume":"14","author":"Li","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"797","DOI":"10.3390\/v15030797","article-title":"B and T cell epitopes of the incursionary foot-and-mouth disease virus serotype SAT2 for vaccine development","volume":"15","author":"Li","year":"2023","journal-title":"Viruses"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.molmed.2019.10.002","article-title":"Tailoring mRNA vaccine to balance innate\/adaptive immune response","volume":"26","author":"Linares-Fern\u00e1ndez","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.3390\/vaccines10111817","article-title":"Development of foot-and-mouth disease vaccines in recent years","volume":"10","author":"Lu","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.3390\/v15061351","article-title":"Comparison of immune responses between inactivated and mRNA SARS-CoV-2 vaccines used for a booster dose in mice","volume":"15","author":"Luan","year":"2023","journal-title":"Viruses"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e4193","DOI":"10.7717\/peerj.4193","article-title":"Spatial pattern of foot-and-mouth disease in animals in China, 2010-2016","volume":"5","author":"Ma","year":"2017","journal-title":"PeerJ"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1080\/14760584.2018.1492378","article-title":"Foot and mouth disease vaccine strain selection: current approaches and future perspectives","volume":"17","author":"Mahapatra","year":"2018","journal-title":"Expert Rev. Vaccines"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/s0168-1702(02)00257-5","article-title":"Molecular basis of pathogenesis of FMDV","volume":"91","author":"Mason","year":"2003","journal-title":"Virus Res."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1016\/s0264-410x(00)00384-4","article-title":"Immune responses and protection against foot-and-mouth disease virus (FMDV) challenge in swine vaccinated with adenovirus-FMDV constructs","volume":"19","author":"Mayr","year":"2001","journal-title":"Vaccine"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/s41590-022-01184-4","article-title":"SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8(+) T cells","volume":"23","author":"Minervina","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"40","DOI":"10.2460\/ajvr.1990.51.01.40","article-title":"Protection of cattle and swine against foot-and-mouth disease, using biosynthetic peptide vaccines","volume":"51","author":"Morgan","year":"1990","journal-title":"Am. J. Vet. Res."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.xphs.2022.11.001","article-title":"The storage and in-use stability of mRNA vaccines and therapeutics: not a cold case","volume":"112","author":"Oude Blenke","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1172\/jci111524","article-title":"Oxygen free radicals in ischemic acute renal failure in the rat","volume":"74","author":"Paller","year":"1984","journal-title":"J. Clin. Invest."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-59745-480-3_2","article-title":"Creation of hybrid nanorods from sequences of natural trimeric fibrous proteins using the fibritin trimerization motif","volume":"474","author":"Papanikolopoulou","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines - a new era in vaccinology","volume":"17","author":"Pardi","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"7806","DOI":"10.1016\/j.vaccine.2007.08.058","article-title":"Reduction of foot-and-mouth disease (FMD) virus load in nasal excretions, saliva and exhaled air of vaccinated pigs following direct contact challenge","volume":"25","author":"Parida","year":"2007","journal-title":"Vaccine"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.7150\/ijbs.59233","article-title":"mRNA vaccines for COVID-19: what, why and how","volume":"17","author":"Park","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.yexmp.2006.12.010","article-title":"A focused salivary gland infection with attenuated MCMV: an animal model with prevention of pathology associated with systemic MCMV infection","volume":"82","author":"Pilgrim","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3390\/vaccines11020386","article-title":"Evaluation of DNA vaccine candidates against foot-and-mouth disease virus in cattle","volume":"11","author":"Puckette","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/s41392-022-01007-w","article-title":"mRNA-based therapeutics: powerful and versatile tools to combat diseases","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1016\/j.cell.2022.03.044","article-title":"Circular RNA vaccines against SARS-CoV-2 and emerging variants","volume":"185","author":"Qu","year":"2022","journal-title":"Cell"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3390\/vaccines9030244","article-title":"An overview on the development of mRNA-based vaccines and their formulation strategies for improved antigen expression in vivo","volume":"9","author":"Rahman","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/tbed.12521","article-title":"Global foot-and-mouth disease research update and gap analysis: 3 - vaccines","volume":"63","author":"Robinson","year":"2016","journal-title":"Transbound. Emerg. Dis."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"D90","DOI":"10.1016\/j.vaccine.2009.08.039","article-title":"Foot and mouth disease virus vaccines","volume":"27","author":"Rodriguez","year":"2009","journal-title":"Vaccine"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1038\/s41587-022-01491-z","article-title":"Unlocking the promise of mRNA therapeutics","volume":"40","author":"Rohner","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1016\/j.vaccine.2021.03.038","article-title":"mRNA vaccines manufacturing: challenges and bottlenecks","volume":"39","author":"Rosa","year":"2021","journal-title":"Vaccine"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/nrd4278","article-title":"mRNA-based therapeutics--developing a new class of drugs","volume":"13","author":"Sahin","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"120586","DOI":"10.1016\/j.ijpharm.2021.120586","article-title":"mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability","volume":"601","author":"Schoenmaker","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"110103","DOI":"10.1016\/j.virol.2024.110103","article-title":"A recombinant multi-epitope trivalent vaccine for foot-and-mouth disease virus serotype O in pigs","volume":"596","author":"Shao","year":"2024","journal-title":"Virology"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1002\/1521-4141(200202)32:2<552::Aid-immu552>3.0.Co;2-h","article-title":"Leptin deficiency, not obesity, protects mice from con A-induced hepatitis","volume":"32","author":"Siegmund","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/vaccines7030090","article-title":"Foot-and-mouth disease virus: Immunobiology, advances in vaccines and vaccination strategies addressing vaccine failures-an Indian perspective","volume":"7","author":"Singh","year":"2019","journal-title":"Vaccines (Basel)"},{"key":"ref78","first-page":"10","article-title":"Production and characterisation of monoclonal antibodies against rabbit attenuated foot-and-mouth disease type O strain YNTBa","volume":"6","author":"Tang","year":"2021","journal-title":"Yunnan J. Anim. Sci. Vet. Med."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.molimm.2003.08.006","article-title":"Optimization of codon pair use within the (GGGGS)3 linker sequence results in enhanced protein expression","volume":"40","author":"Trinh","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.3390\/vaccines9091033","article-title":"Challenges of storage and stability of mRNA-based COVID-19 vaccines","volume":"9","author":"Uddin","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"eadc9937","DOI":"10.1126\/sciadv.adc9937","article-title":"A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets","volume":"8","author":"van de Ven","year":"2022","journal-title":"Sci. Adv."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"16744","DOI":"10.1038\/s41598-023-43898-x","article-title":"Elucidation of lipid nanoparticle surface structure in mRNA vaccines","volume":"13","author":"Wang","year":"2023","journal-title":"Sci. Rep."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12943-021-01311-z","article-title":"mRNA vaccine: a potential therapeutic strategy","volume":"20","author":"Wang","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1080\/22221751.2022.2030200","article-title":"Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 omicron variant escape from neutralizing antibodies","volume":"11","author":"Wang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1016\/j.vaccine.2018.02.016","article-title":"Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging a\/ASIA\/G-VII lineage","volume":"36","author":"Waters","year":"2018","journal-title":"Vaccine"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/nbt.3301","article-title":"Mammalian synthetic circuits with RNA binding proteins for RNA-only delivery","volume":"33","author":"Wroblewska","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"e2119995119","DOI":"10.1073\/pnas.2119995119","article-title":"Glycosite-deleted mRNA of SARS-CoV-2 spike protein as a broad-spectrum vaccine","volume":"119","author":"Wu","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"2256422","DOI":"10.1080\/22221751.2023.2256422","article-title":"An mRNA-based broad-spectrum vaccine candidate confers cross-protection against heterosubtypic influenza a viruses","volume":"12","author":"Xiong","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"729","DOI":"10.3390\/pathogens9090729","article-title":"Molecular mechanisms of immune escape for foot-and-mouth disease virus","volume":"9","author":"Yang","year":"2020","journal-title":"Pathogens"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1099\/jgv.0.000911","article-title":"ICTV virus taxonomy profile: Picornaviridae","volume":"98","author":"Zell","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"e0295823","DOI":"10.1128\/mbio.02958-23","article-title":"PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge","volume":"15","author":"Zhao","year":"2024","journal-title":"MBio"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1139\/cjm-2018-0090","article-title":"Corrigendum: foot-and-mouth disease virus infection stimulates innate immune signaling in the mouse macrophage RAW 264.7 cells","volume":"64","author":"Zhi","year":"2018","journal-title":"Can. J. Microbiol."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1080\/15476286.2019.1700058","article-title":"NLRP3 inflammasome activation by foot-and-mouth disease virus infection mainly induced by viral RNA and non-structural protein 2B","volume":"17","author":"Zhi","year":"2020","journal-title":"RNA Biol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"8454","DOI":"10.1128\/jvi.00163-16","article-title":"Reversion of cold-adapted live attenuated influenza vaccine into a pathogenic virus","volume":"90","author":"Zhou","year":"2016","journal-title":"J. Virol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1038\/s41467-022-30340-5","article-title":"Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 omicron variant","volume":"13","author":"Zuo","year":"2022","journal-title":"Nat. Commun."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1503191\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T12:02:49Z","timestamp":1745841769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1503191\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":96,"alternative-id":["10.3389\/fmicb.2025.1503191"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1503191","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"article-number":"1503191"}}