{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:25:13Z","timestamp":1782170713711,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["309455"],"award-info":[{"award-number":["309455"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["FiDiPro grant NOVAC Dnro 1913\/31\/2012"],"award-info":[{"award-number":["FiDiPro grant NOVAC Dnro 1913\/31\/2012"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014438","name":"Business Finland","doi-asserted-by":"publisher","award":["THERDIAB 1843\/31\/2014"],"award-info":[{"award-number":["THERDIAB 1843\/31\/2014"]}],"id":[{"id":"10.13039\/501100014438","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tthe Swedish Medical Research Council","award":["2017-02020"],"award-info":[{"award-number":["2017-02020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL\/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.<\/jats:p>","DOI":"10.3390\/microorganisms8091287","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T10:37:32Z","timestamp":1598265452000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-1248","authenticated-orcid":false,"given":"Minna M.","family":"Hankaniemi","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo A.","family":"Baikoghli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA"},{"name":"Institute for Molecular Medicine Finland (FIMM), HiLIFE, P.O. Box 20, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia M.","family":"Stone","sequence":"additional","affiliation":[{"name":"The Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"V\u00e4\u00e4t\u00e4inen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saana","family":"Soppela","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5538-5153","authenticated-orcid":false,"given":"Amirbabak","family":"Sioofy-Khojine","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-974X","authenticated-orcid":false,"given":"Niila V. V.","family":"Saarinen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Anson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Hy\u00f6ty","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"},{"name":"Fimlab Laboratories, FI-33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4592-5926","authenticated-orcid":false,"given":"Varpu","family":"Marjom\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Science\/Nanoscience Center, University of Jyv\u00e4skyl\u00e4, P.O. Box 35, FI-40014 Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-2052","authenticated-orcid":false,"given":"Malin","family":"Flodstr\u00f6m-Tullberg","sequence":"additional","affiliation":[{"name":"The Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2068-7271","authenticated-orcid":false,"given":"R. Holland","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-1480","authenticated-orcid":false,"given":"Vesa P.","family":"Hyt\u00f6nen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"},{"name":"Fimlab Laboratories, FI-33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3751-9952","authenticated-orcid":false,"given":"Olli H.","family":"Laitinen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Tampere University, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.virol.2015.06.006","article-title":"Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis","volume":"484","author":"Sin","year":"2015","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.33594\/000000125","article-title":"A kidnapping story: How Coxsackievirus B3 and its host cell interact","volume":"53","author":"Peischard","year":"2019","journal-title":"Cell. 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