{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:37:28Z","timestamp":1767836248629,"version":"3.49.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,18]],"date-time":"2024-02-18T00:00:00Z","timestamp":1708214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Engineering in Life Sciences"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Innovations in viral vaccine manufacturing are crucial for pandemic preparedness and to meet ever\u2010rising global demands. For influenza, however, production still mainly relies on technologies established decades ago. Although modern production shifts from egg\u2010based towards cell culture technologies, the full potential has not yet been fully exploited. Here, we evaluate whether implementation of state\u2010of\u2010the\u2010art technologies for cell culture\u2010based recombinant protein production are capable to challenge outdated approaches in viral vaccine process development. For this, a fully automated single\u2010cell cloning strategy was established to generate monoclonal suspension Madin\u2010Darby canine kidney (MDCK) cells. Among selected cell clones, we could observe distinct metabolic and growth characteristics, with C59 reaching a maximum viable cell concentration of 17.3 \u00d7 10<jats:sup>6<\/jats:sup> cells\/mL and low doubling times in batch mode. Screening for virus production using a panel of human vaccine\u2010relevant influenza A and B viruses in an ambr15 system revealed high titers with yields competing or even outperforming available MDCK cell lines. With C113, we achieved cell\u2010specific virus yields of up to 25,000 virions\/cell, making this cell clone highly attractive for vaccine production. Finally, we confirmed process performance at a 50\u2010fold higher working volume. In summary, we present a scalable and powerful approach for accelerated development of high\u2010yield influenza virus production in chemically defined medium starting from a single cell.<\/jats:p>","DOI":"10.1002\/elsc.202300245","type":"journal-article","created":{"date-parts":[[2024,2,18]],"date-time":"2024-02-18T23:46:28Z","timestamp":1708299988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["From single\u2010cell cloning to high\u2010yield influenza virus production \u2013 implementing advanced technologies in vaccine process development"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9514-3069","authenticated-orcid":false,"given":"Tilia","family":"Zinnecker","sequence":"first","affiliation":[{"name":"Max Planck Institute for Dynamics of Complex Technical Systems  Magdeburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najd","family":"Badri","sequence":"additional","affiliation":[{"name":"Sartorius Stedim Cellca GmbH  Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diogo","family":"Araujo","sequence":"additional","affiliation":[{"name":"Sartorius Stedim Biotech S.A. Aubagne Cedex France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Thiele","sequence":"additional","affiliation":[{"name":"Sartorius Stedim Cellca GmbH  Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-1332","authenticated-orcid":false,"given":"Udo","family":"Reichl","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Dynamics of Complex Technical Systems  Magdeburg Germany"},{"name":"Bioprocess Engineering Otto\u2010von\u2010Guericke University  Magdeburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-5943","authenticated-orcid":false,"given":"Yvonne","family":"Genzel","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Dynamics of Complex Technical Systems  Magdeburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.12.018"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11010052"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1016666"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjce.24197"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.31"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.06.021"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2021.02.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2548"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-022-12027-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141686"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.04.054"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-010-2742-9"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-11-84"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-12-79"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00508-9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv091"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-012-4238-2"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.03.102"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.04.030"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.11.023"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075014"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9938"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.128"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-11050-8"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2007.10.002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-733-4_23"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27876"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-6-162"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2016.01.001"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202100165"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2012.06.005"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2010.04.003"},{"key":"e_1_2_10_34_1","unstructured":"BissingerT.Evaluation of MDCK suspension cell lines for influenza A virus production: media metabolism and process conditions. Doctoral dissertation Otto\u2010von\u2010Guericke\u2010Universit\u00e4t Magdeburg.2020."},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(95)00196-4"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02922022"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-1-137"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2003.11.041"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2594"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.05.083"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9050426"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2013.04.011"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-012-9446-1"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2019.1598230"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1874"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2162"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3277"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28088"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-019-00346-x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28530"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.11.044"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.09.051"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.02.016"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00672"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-018-0079-z"}],"container-title":["Engineering in Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/elsc.202300245","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T09:13:47Z","timestamp":1760519627000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/elsc.202300245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,18]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/elsc.202300245"],"URL":"https:\/\/doi.org\/10.1002\/elsc.202300245","archive":["Portico"],"relation":{},"ISSN":["1618-0240","1618-2863"],"issn-type":[{"value":"1618-0240","type":"print"},{"value":"1618-2863","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,18]]},"assertion":[{"value":"2023-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2300245"}}