{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:24:36Z","timestamp":1768717476419,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Virus\u2010like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP\u2010based anti\u2010sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB\/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic <jats:italic>Plasmodium berghei<\/jats:italic> parasites. Here, we have modified the preclinical production process to enable the production of sufficient quantities of highly pure, clinical\u2010grade material for use in human clinical trials. The R21 construct was re\u2010engineered to include a C\u2010tag to allow affinity\u2010based separation from the major contaminant alcohol oxidase 1 (AOX 1, ~74\u2009kDa). To our knowledge, this is the first use of C\u2010tag technology to purify a VLP vaccine candidate for use in human clinical trials. The R21 vaccine has shown high\u2010level efficacy in an African Phase IIb trial, and multiple clinical trials are underway to assess the safety and efficacy of the vaccine. Our findings support the future use of C\u2010tag platform technologies to enable cGMP\u2010compliant biomanufacturing of high purity yeast\u2010expressed VLP\u2010based vaccines for early phase clinical trials when clinical grade material is required in smaller quantities in a quick time frame.<\/jats:p>","DOI":"10.1002\/bit.28181","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T06:12:16Z","timestamp":1657692736000},"page":"2784-2793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Production of a high purity, C\u2010tagged hepatitis B surface antigen fusion protein VLP vaccine for malaria expressed in <i>Pichia pastoris<\/i> under cGMP conditions"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-2522","authenticated-orcid":false,"given":"Ekta","family":"Mukhopadhyay","sequence":"first","affiliation":[{"name":"Clinical 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D.","family":"Tarrant","sequence":"additional","affiliation":[{"name":"Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J.","family":"Detmers","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma J.","family":"Bolam","sequence":"additional","affiliation":[{"name":"Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioana N.","family":"Baleanu","sequence":"additional","affiliation":[{"name":"Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford 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UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah C.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon J.","family":"Draper","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah P.","family":"Moyle","sequence":"additional","affiliation":[{"name":"Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine University of Oxford Oxford 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