{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:24:37Z","timestamp":1780475077039,"version":"3.54.1"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007750","name":"National Cheng Kung University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020953","name":"Taiwan Centers for Disease Control","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020953","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["10A1-IVPP16-014"],"award-info":[{"award-number":["10A1-IVPP16-014"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["11A1-IVPP14\\u2013014"],"award-info":[{"award-number":["11A1-IVPP14\\u2013014"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["12A1-IVPP18-014"],"award-info":[{"award-number":["12A1-IVPP18-014"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["13A1-IVPP20-014"],"award-info":[{"award-number":["13A1-IVPP20-014"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005057","name":"National Tsing Hua University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Vaccine: X"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1016\/j.jvacx.2024.100559","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T13:35:59Z","timestamp":1726752959000},"page":"100559","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Enhanced production of recombinant coxsackievirus A16 using a serum-free HEK293A suspension culture system for bivalent enterovirus vaccine development"],"prefix":"10.1016","volume":"20","author":[{"given":"Yi-An","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Sheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yeu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7043-3148","authenticated-orcid":false,"given":"Ting-Ting","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Rung","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Ren","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1672-5255","authenticated-orcid":false,"given":"Suh-Chin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-0389","authenticated-orcid":false,"given":"Chia-Chyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jvacx.2024.100559_b0005","doi-asserted-by":"crossref","first-page":"360","DOI":"10.4161\/hv.27087","article-title":"Coxsackievirus A16: Epidemiology, diagnosis and vaccine","volume":"10","author":"Mao","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"10.1016\/j.jvacx.2024.100559_b0010","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1080\/21645515.2015.1049780","article-title":"Is a multivalent hand, foot, and mouth disease vaccine feasible?","volume":"11","author":"Klein","year":"2015","journal-title":"Hum Vaccin Immunother"},{"key":"10.1016\/j.jvacx.2024.100559_b0015","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1080\/14760584.2018.1510326","article-title":"Recent development of enterovirus A vaccine candidates for the prevention of hand, foot, and mouth disease","volume":"17","author":"Fang","year":"2018","journal-title":"Expert Rev Vaccines"},{"key":"10.1016\/j.jvacx.2024.100559_b0020","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/17460441.2021.1965987","article-title":"Novel strategies for the development of hand, foot, and mouth disease vaccines and antiviral therapies","volume":"17","author":"Fang","year":"2022","journal-title":"Expert Opin Drug Discov"},{"key":"10.1016\/j.jvacx.2024.100559_b0025","doi-asserted-by":"crossref","first-page":"e49973","DOI":"10.1371\/journal.pone.0049973","article-title":"Immunological and biochemical characterization of coxsackie virus A16 viral particles","volume":"7","author":"Chong","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jvacx.2024.100559_b0030","doi-asserted-by":"crossref","first-page":"6642","DOI":"10.1016\/j.vaccine.2012.08.071","article-title":"A virus-like particle vaccine for coxsackievirus A16 potently elicits neutralizing antibodies that protect mice against lethal challenge","volume":"30","author":"Liu","year":"2012","journal-title":"Vaccine"},{"key":"10.1016\/j.jvacx.2024.100559_b0035","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.vaccine.2013.03.007","article-title":"Active immunization with a Coxsackievirus A16 experimental inactivated vaccine induces neutralizing antibodies and protects mice against lethal infection","volume":"31","author":"Cai","year":"2013","journal-title":"Vaccine"},{"key":"10.1016\/j.jvacx.2024.100559_b0040","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.4161\/hv.28083","article-title":"Comparative study of the immunogenicity in mice and monkeys of an inactivated CA16 vaccine made from a human diploid cell line","volume":"10","author":"Yang","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"10.1016\/j.jvacx.2024.100559_b0045","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/670506","article-title":"Immunogenicity studies of bivalent inactivated virions of EV71\/CVA16 formulated with submicron emulsion systems","volume":"2014","author":"Lin","year":"2014","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.jvacx.2024.100559_b0050","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.4161\/hv.29823","article-title":"Evaluation of monovalent and bivalent vaccines against lethal Enterovirus 71 and Coxsackievirus A16 infection in newborn mice","volume":"10","author":"Sun","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"10.1016\/j.jvacx.2024.100559_b0055","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1080\/22221751.2020.1823889","article-title":"Immune responses of a CV-A16 live attenuated candidate strain and its protective effects in rhesus monkeys","volume":"9","author":"Yang","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"10.1016\/j.jvacx.2024.100559_b0060","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.virol.2016.10.031","article-title":"Pathologic and immunologic characteristics of coxsackievirus A16 infection in rhesus macaques","volume":"500","author":"Wang","year":"2017","journal-title":"Virology"},{"key":"10.1016\/j.jvacx.2024.100559_b0065","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1080\/21645515.2018.1426420","article-title":"Poorly neutralizing polyclonal antibody in vitro against coxsackievirus A16 circulating strains can prevent a lethal challenge in vivo","volume":"14","author":"Yao","year":"2018","journal-title":"Hum Vaccin Immunother"},{"key":"10.1016\/j.jvacx.2024.100559_b0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.virusres.2023.199101","article-title":"Propagation and immunological characterization of coxsackievirus A10 in a serum-free HEK293A cell culture system","volume":"329","author":"Lien","year":"2023","journal-title":"Virus Res"},{"issue":"22","key":"10.1016\/j.jvacx.2024.100559_b0075","doi-asserted-by":"crossref","first-page":"10342","DOI":"10.1073\/pnas.88.22.10342","article-title":"Construction of intertypic chimeric dengue viruses by substitution of structural protein genes","volume":"88","author":"Bray","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jvacx.2024.100559_b0080","doi-asserted-by":"crossref","first-page":"16825","DOI":"10.1073\/pnas.0505587102","article-title":"An improved reverse genetics system for influenza A virus generation and its implications for vaccine production","volume":"102","author":"Neumann","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jvacx.2024.100559_b0085","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.antiviral.2016.06.014","article-title":"Development of a full-length cDNA-derived enterovirus A71 vaccine candidate using reverse genetics technology","volume":"132","author":"Yang","year":"2016","journal-title":"Antiviral Res"},{"key":"10.1016\/j.jvacx.2024.100559_b0090","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.chom.2020.04.004","article-title":"An Infectious cDNA Clone of SARS-CoV-2","volume":"27","author":"Xie","year":"2020","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.jvacx.2024.100559_b0095","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3390\/ijms18010020","article-title":"Reverse Genetics Approaches for the Development of Influenza Vaccines","volume":"18","author":"Nogales","year":"2016","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jvacx.2024.100559_b0100","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/1743-422X-8-534","article-title":"Construction and characterization of an infectious clone of coxsackievirus A16","volume":"8","author":"Liu","year":"2011","journal-title":"Virol J"},{"key":"10.1016\/j.jvacx.2024.100559_b0105","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12250-015-3610-7","article-title":"Development and characterization of a clinical strain of Coxsackievirus A16 and an eGFP infectious clone","volume":"30","author":"Deng","year":"2015","journal-title":"Virol Sin"},{"key":"10.1016\/j.jvacx.2024.100559_b0110","doi-asserted-by":"crossref","first-page":"20839","DOI":"10.1038\/srep20839","article-title":"Identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of Coxsackievirus A16","volume":"6","author":"Li","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.jvacx.2024.100559_b0115","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s12250-016-3716-6","article-title":"Improved plasmid-based recovery of coxsackievirus A16 infectious clone driven by human RNA polymerase I promoter","volume":"31","author":"Wang","year":"2016","journal-title":"Virol Sin"},{"key":"10.1016\/j.jvacx.2024.100559_b0120","doi-asserted-by":"crossref","first-page":"1101850","DOI":"10.3389\/fmicb.2022.1101850","article-title":"The development and characterization of a stable Coxsackievirus A16 infectious clone with Nanoluc reporter gene","volume":"13","author":"Yu","year":"2023","journal-title":"Front Microbiol"},{"key":"10.1016\/j.jvacx.2024.100559_b0125","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.virs.2024.03.004","article-title":"Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research","volume":"39","author":"Yu","year":"2024","journal-title":"Virol Sin"},{"key":"10.1016\/j.jvacx.2024.100559_b0130","doi-asserted-by":"crossref","first-page":"e00298","DOI":"10.1128\/CVI.00298-16","article-title":"Multivalent and Multipathogen Viral Vector Vaccines","volume":"24","author":"Lauer","year":"2017","journal-title":"Clin Vaccine Immunol"},{"key":"10.1016\/j.jvacx.2024.100559_b0135","doi-asserted-by":"crossref","first-page":"e79783","DOI":"10.1371\/journal.pone.0079783","article-title":"Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers","volume":"8","author":"Chou","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jvacx.2024.100559_b0140","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1016\/j.vaccine.2014.08.064","article-title":"Prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases","volume":"32","author":"Liu","year":"2014","journal-title":"Vaccine"},{"issue":"11","key":"10.1016\/j.jvacx.2024.100559_b0145","doi-asserted-by":"crossref","first-page":"5919","DOI":"10.3390\/v7112916","article-title":"Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice","volume":"7","author":"Caine","year":"2015","journal-title":"Viruses"},{"key":"10.1016\/j.jvacx.2024.100559_b0150","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.antiviral.2016.02.008","article-title":"Immunological and biochemical characterizations of coxsackievirus A6 and A10 viral particles","volume":"129","author":"Liu","year":"2016","journal-title":"Antiviral Res"},{"key":"10.1016\/j.jvacx.2024.100559_b0155","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3390\/ijms24010169","article-title":"Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines","volume":"24","author":"Zhang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.jvacx.2024.100559_b0160","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.jmii.2023.10.006","article-title":"The stability and immunogenicity of formalin-inactivated Enterovirus A71 whole virion vaccine after ten years of low temperature storage","volume":"56","author":"Shen","year":"2023","journal-title":"J Microbiol Immunol Infect"},{"key":"10.1016\/j.jvacx.2024.100559_b0165","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1128\/MMBR.05023-11","article-title":"Viral quasispecies evolution","volume":"76","author":"Domingo","year":"2012","journal-title":"Microbiol Mol Biol Rev"},{"key":"10.1016\/j.jvacx.2024.100559_b0170","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41541-021-00358-9","article-title":"Haplotype-resolved de novo assembly of the Vero cell line genome","volume":"6","author":"S\u00e8ne","year":"2021","journal-title":"npj Vaccines"},{"key":"10.1016\/j.jvacx.2024.100559_b0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.biotechadv.2020.107608","article-title":"Vero cell upstream bioprocess development for the production of viral vectors and vaccines","volume":"44","author":"Kiesslich","year":"2020","journal-title":"Biotechnol Adv"},{"key":"10.1016\/j.jvacx.2024.100559_b0180","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3109\/07388551.2015.1084266","article-title":"Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives","volume":"36","author":"Dumont","year":"2016","journal-title":"Crit Rev Biotechnol"},{"key":"10.1016\/j.jvacx.2024.100559_b0185","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1056\/NEJMoa2105290","article-title":"Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine","volume":"385","author":"Falsey","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jvacx.2024.100559_b0190","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.1038\/s41598-021-84891-6","article-title":"Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16","volume":"11","author":"Wang","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.jvacx.2024.100559_b0195","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1080\/22221751.2022.2093132","article-title":"Development and evaluation of an inactivated coxsackievirus A16 vaccine in gerbils","volume":"11","author":"Sun","year":"2022","journal-title":"Emerg Microbes Infect"},{"key":"10.1016\/j.jvacx.2024.100559_b0200","doi-asserted-by":"crossref","first-page":"6055","DOI":"10.1016\/j.vaccine.2023.08.029","article-title":"Potential of a bivalent vaccine for broad protection against enterovirus 71 and coxsackie virus 16 infections causing hand, foot, and mouth disease","volume":"41","author":"Yi","year":"2023","journal-title":"Vaccine"}],"container-title":["Vaccine: X"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590136224001323?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590136224001323?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T19:29:33Z","timestamp":1729020573000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2590136224001323"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":40,"alternative-id":["S2590136224001323"],"URL":"https:\/\/doi.org\/10.1016\/j.jvacx.2024.100559","relation":{},"ISSN":["2590-1362"],"issn-type":[{"value":"2590-1362","type":"print"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Enhanced production of recombinant coxsackievirus A16 using a serum-free HEK293A suspension culture system for bivalent enterovirus vaccine development","name":"articletitle","label":"Article Title"},{"value":"Vaccine: X","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jvacx.2024.100559","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"100559"}}