{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:52:00Z","timestamp":1791341520238,"version":"4.3.1"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including tuberculosis and COVID-19. Cost-effective and scalable biomanufacturing processes are critical for the commercialization of adenovirus-vectored vaccines. Adenoviral vectors are commonly produced through the infection of batch cultures at low cell density cultures, mostly because infections at high cell densities result in reduced cell-specific virus productivity and does not improve volumetric productivity. In this study, we have investigated the feasibility of improving the volumetric productivity by infecting fed-batch cultures at high cell densities. Four commercial and one in-house developed serum-free media were first tested for supporting growth of HEK 293 cells and production of adenovirus type 5 (Ad5) in batch culture. Two best media were then selected for development of fed-batch culture to improve cell growth and virus productivity. A maximum viable cell density up to 16 \u00d7 106 cells\/mL was achieved in shake flask fed-batch cultures using the selected media and commercial or in-house developed feeds. The volumetric virus productivity was improved by up to six folds, reaching 3.0 \u00d7 1010 total viral particles\/mL in the fed-batch culture cultivated with the media and feeds developed in house and infected at a cell density of 5 \u00d7 106 cells\/mL. Additional rounds of optimization of media and feed were required to maintain the improved titer when the fed-batch culture was scaled up in a bench scale (3 L) bioreactor. Overall, the results suggested that fed-batch culture is a simple and feasible process to significantly improve the volumetric productivity of Ad5 through optimization and balance of nutrients in culture media and feeds.<\/jats:p>","DOI":"10.3390\/vaccines12050524","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T09:22:52Z","timestamp":1715332972000},"page":"524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Optimization of Culture Media and Feeding Strategy for High Titer Production of an Adenoviral Vector in HEK 293 Fed-Batch Culture"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-3170","authenticated-orcid":false,"given":"Chun Fang","family":"Shen","sequence":"first","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Rodenbrock","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Lanthier","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Burney","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Loignon","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada, Montreal, QC H4P 2R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.ymthe.2022.01.034","article-title":"Adenovirus-based vaccines-a platform for pandemic preparedness against emerging viral pathogens","volume":"30","author":"Coughlan","year":"2022","journal-title":"Mol. 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