{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:48:51Z","timestamp":1792586931888,"version":"4.5.0"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["899670"],"award-info":[{"award-number":["899670"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006366","name":"Minist\u00e9rio da Educa\u00e7\u00e3o","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biotechnology"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.jbiotec.2026.09.009","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T15:08:43Z","timestamp":1789225723000},"page":"83-93","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Process intensification for production of Adenovirus-like particles (ADDomer) as snake-bite therapy"],"prefix":"10.1016","volume":"420","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9855-4877","authenticated-orcid":false,"given":"Birhanu","family":"Hurisa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-7974","authenticated-orcid":false,"given":"Ricardo","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-9045","authenticated-orcid":false,"given":"Imre","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1516-9760","authenticated-orcid":false,"given":"Christiane","family":"Schaffitzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6606-8903","authenticated-orcid":false,"given":"Yimtubezinash","family":"Woldeamanuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-4899","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Rold\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbiotec.2026.09.009_bib1","first-page":"14","article-title":"Recommendations for comparison of productivity between fed-batch and perfusion processes","author":"Bausch","year":"2019","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/bit.22364","article-title":"Cell density effect in the baculovirus-insect cells system: a quantitative analysis of energetic metabolism","volume":"104","author":"Bernal","year":"2009","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib3","doi-asserted-by":"crossref","unstructured":"Caron, A.W., Archarnbault, J., Massie, B., 1990. High-Level Recombinant Protein Production in Bioreactors Using the Baculovirus-Insect Cell Expression System.","DOI":"10.1002\/bit.260361108"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib4","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/0041-0101(91)90116-9","article-title":"Snake venom variability: methods of study, results and interpretation","volume":"29","author":"Chippaux","year":"1991","journal-title":"Toxicon"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib5","first-page":"1","article-title":"Improving influenza HA-VLPs production in insect high five cells via adaptive laboratory evolution","volume":"8","author":"Correia","year":"2020","journal-title":"Vaccin. (Basel)"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib6","first-page":"1","article-title":"Improving influenza HA-VLPs production in insect high five cells via adaptive laboratory evolution","volume":"8","author":"Correia","year":"2020","journal-title":"Vaccin. (Basel)"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib7","doi-asserted-by":"crossref","DOI":"10.1002\/bit.28925","article-title":"Continuous Production of Influenza VLPs Using IC-BEVS and Multi-Stage Bioreactors","author":"Correia","year":"2025","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib8","first-page":"39","article-title":"Current challenges and recent advances on the path towards continuous biomanufacturing","author":"Drobnjakovic","year":"2023","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib9","first-page":"10","article-title":"Intensifying continuous production of Gag-HA VLPs at high cell density using stable insect cells adapted to low culture temperature","author":"Fernandes","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib10","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1002\/bit.27766","article-title":"Integrating high cell density cultures with adapted laboratory evolution for improved Gag-HA virus-like particles production in stable insect cell lines","volume":"118","author":"Fernandes","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.tibtech.2018.08.008","article-title":"The current scientific and regulatory landscape in advancing integrated continuous biopharmaceutical manufacturing","volume":"37","author":"Fisher","year":"2019","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib12","first-page":"3","article-title":"Snakebite envenoming","author":"Guti\u00e9rrez","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.coche.2018.09.009","article-title":"Continuous manufacturing of viral particles","author":"Guti\u00e9rrez-Granados","year":"2018","journal-title":"Curr. Opin. Chem. Eng."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib14","doi-asserted-by":"crossref","unstructured":"Ikonomou, L., 2004. Effect of partial medium replacement on cell growth and protein production for the High-Five TM insect cell line.","DOI":"10.1023\/B:CYTO.0000043413.53044.fa"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib15","doi-asserted-by":"crossref","DOI":"10.1007\/s00253-003-1223-9","article-title":"Insect cell culture for industrial production of recombinant proteins","author":"Ikonomou","year":"2003","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib16","doi-asserted-by":"crossref","DOI":"10.1007\/BF00350399","article-title":"Perfusion bioreactors for the production of recombinant proteins in insect cells","author":"J\u00e4ger","year":"1996","journal-title":"Cytotechnology"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/B978-0-7506-1845-8.50050-8","article-title":"High density insect cell culture for the production of recombinant proteins with the baculovirus expression system","author":"J\u00e4ger","year":"1994","journal-title":"Anim. Cell. Technol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib18","first-page":"8","article-title":"Cost of manufacturing for recombinant snakebite antivenoms","author":"Jenkins","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.copbio.2017.12.015","article-title":"Continuous integrated manufacturing of therapeutic proteins","volume":"53","author":"Karst","year":"2018","journal-title":"Curr. Opin. Biotechnol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib20","article-title":"Perfusion process intensification for lentivirus production using a novel scale-down model","author":"Klimpel","year":"2024","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib21","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/jps.24268","article-title":"White paper on continuous bioprocessing may 20\u201321 2014 continuous manufacturing symposium","volume":"104","author":"Konstantinov","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.biotechadv.2022.108017","article-title":"The cell density effect in animal cell-based bioprocessing: questions, insights and perspectives","author":"Lavado-Garc\u00eda","year":"2022","journal-title":"Biotechnol. Adv."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib23","doi-asserted-by":"crossref","DOI":"10.1201\/9780429054204-2","article-title":"Handbook of venoms and toxins of reptiles","author":"Mackessy","year":"2021","journal-title":"Second. Edi. Ed. Handb. Venoms Toxins Reptiles"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib24","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2144\/03342bm05","article-title":"Titration of non-occluded baculovirus using a cell viability assay","volume":"34","author":"Mena","year":"2003","journal-title":"Biotechniques"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib25","first-page":"15","article-title":"ADDovenom: thermostable protein-based ADDomer nanoparticles as new therapeutics for snakebite envenoming","author":"Menzies","year":"2023","journal-title":"Toxins (Basel)"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib26","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/bit.24608","article-title":"Fed-batch and perfusion culture processes: economic, environmental, and operational feasibility under uncertainty","volume":"110","author":"Pollock","year":"2013","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/cite.201200121","article-title":"Increase of protein yield in high five cells in a single-use perfusion bioreactor by medium replacement","volume":"85","author":"Rausch","year":"2013","journal-title":"Chem. Ing. Tech."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jviromet.2009.03.007","article-title":"Error assessment in recombinant baculovirus titration: evaluation of different methods","volume":"159","author":"Rold\u00e3o","year":"2009","journal-title":"J. Virol. Methods"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib29","doi-asserted-by":"crossref","DOI":"10.1007\/s00253-015-7267-9","article-title":"Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production","author":"Tapia","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib30","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/S0140-6736(05)74319-1","article-title":"Crisis in snake antivenom supply for Africa","volume":"356","author":"Theakston","year":"2000","journal-title":"Lancet"},{"key":"10.1016\/j.jbiotec.2026.09.009_bib31","article-title":"Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display","author":"Vragniau","year":"2019","journal-title":"Sci. Synth."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib32","first-page":"38","article-title":"New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India","volume":"138","author":"Warrell","year":"2013","journal-title":"Indian. J. Med. Res."},{"key":"10.1016\/j.jbiotec.2026.09.009_bib33","first-page":"192","article-title":"Guidelines for the production, control and regulation of snake antivenom immunoglobulins, Annex 5, TRS No 1004","author":"WHO","year":"2013","journal-title":"WHO Tech. Report. Ser."}],"container-title":["Journal of Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168165626002555?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168165626002555?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:31:29Z","timestamp":1792585889000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168165626002555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":33,"alternative-id":["S0168165626002555"],"URL":"https:\/\/doi.org\/10.1016\/j.jbiotec.2026.09.009","relation":{},"ISSN":["0168-1656"],"issn-type":[{"value":"0168-1656","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Process intensification for production of Adenovirus-like particles (ADDomer) as snake-bite therapy","name":"articletitle","label":"Article Title"},{"value":"Journal of Biotechnology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbiotec.2026.09.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}