{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:43Z","timestamp":1787027623652,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biology"],"abstract":"<jats:p>The rabies virus remains a significant public health threat, particularly in regions with limited access to vaccination. This study shows that the BelloStage\u2122-3000 bioreactor, operating on the \u201cTide Motion\u201d principle, in combination with BioNOC\u00ae II macrocarriers, ensures highly efficient rabies virus cultivation in BSR and Vero cells grown in serum-free OptiPRO\u2122 SFM medium. This system supports effective cell attachment, formation of a dense and metabolically active cell layer, and reduces microbial contamination risks associated with serum-containing media. For comparison, rabies virus cultivation was also performed on Cytodex 1 and Cytodex 3 microcarriers in spinner flasks. The use of the BelloStage\u2122-3000 bioreactor system with BelloCell\u2122 500A disposable vials and BioNOC II\u00ae macrocarriers resulted in significantly higher virus titers compared to traditional Cytodex 1 and Cytodex 3 microcarrier culture systems. Thus, in the BSR cell culture, the maximum virus titer reached 5.6 \u00d7 108 FFU\/mL by day 4 of cultivation, which exceeded the titers obtained on Cytodex 1 and Cytodex 3 microcarriers by about 19.3-fold and 15.3-fold, respectively. A similar trend was observed for the Vero cell line: the peak titer was 2.0 \u00d7 108 FFU\/mL by day 5 of culturing, which was higher than the values obtained on Cytodex 1 and Cytodex 3 by about 14.0-fold and 9.6-fold, respectively. These findings demonstrate that the integrated use of BioNOC\u00ae II macrocarriers, the BelloStage\u2122-3000 bioreactor, and a serum-free medium provides a scalable, reproducible, and biosafe platform for rabies virus production, offering substantial advantages over traditional microcarrier-based systems.<\/jats:p>","DOI":"10.3390\/biology14101455","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:17:35Z","timestamp":1761056255000},"page":"1455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficient Serum-Free Rabies Virus Propagation Using BSR and Vero Cell Lines: A Comparative Evaluation of BioNOC II\u00ae Macrocarriers in the BelloStage\u2122-3000 Bioreactor Versus Conventional Microcarriers"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhanat","family":"Amanova","sequence":"first","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2332-2841","authenticated-orcid":false,"given":"Zhanna","family":"Sametova","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-0655","authenticated-orcid":false,"given":"Sholpan","family":"Turyskeldy","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9484-0540","authenticated-orcid":false,"given":"Alina","family":"Kurmasheva","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-2491","authenticated-orcid":false,"given":"Ruslan","family":"Abitayev","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-3793","authenticated-orcid":false,"given":"Abdurakhman","family":"Ussembay","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding 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