{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:12:41Z","timestamp":1787620361201,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health of the Republic of Kazakhstan","award":["IRN BR25293294"],"award-info":[{"award-number":["IRN BR25293294"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Brucellosis remains one of the most significant zoonotic diseases, posing a serious threat to both human health and livestock. This issue is particularly relevant for Kazakhstan, which is among the countries endemic for brucellosis with a high incidence rate. Such circumstances highlight the urgent need for the development and implementation of effective preventive measures, including modern vaccine platforms capable of providing reliable protection for the population and reducing the economic impact on the agricultural sector. Recombinant capripoxviruses are considered promising vector platforms for vaccine development, as they ensure high expression of target antigens, elicit strong immune responses, and are safe for humans. In this study, the replication of recombinant capripoxviruses expressing Brucella antigens (SPPV (TK-) OMP19\/SODC and SPPV (TK-) OMP25) was evaluated in Vero cells using the BelloStage\u2122-3000 bioreactor system in combination with BioNOC II\u00ae macrocarriers. Application of the bioreactor resulted in nearly a 100-fold increase in Vero cell density compared with static cultures and provided optimal conditions for cell adhesion, growth, and metabolic activity. Consequently, a significant increase in viral titers was observed: for SPPV (TK-) OMP19\/SODC, mean titers reached 7.50 log10 TCID50\/mL versus 4.50 in static culture (p &lt; 0.0001), while SPPV (TK-) OMP25 achieved 7.08 log10 TCID50\/mL versus 4.33 (p &lt; 0.001). These findings confirm the reliability, reproducibility, and scalability of this bioreactor-based approach, demonstrating clear advantages over conventional cultivation methods. Overall, the study highlights the high potential of the BelloStage\u2122-3000 system with BioNOC II\u00ae macrocarriers for the industrial production of recombinant capripoxvirus-based vaccines against brucellosis and for the broader development of other recombinant viral vaccines.<\/jats:p>","DOI":"10.3390\/cells14201631","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:44:10Z","timestamp":1760957050000},"page":"1631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["BelloStage\u2122-3000 Bioreactor Versus Conventional Cultivation of Recombinant Capripoxvirus Expressing Brucella Antigens in Vero Cells: A Step Towards the Development of a New Human Brucellosis Vaccine"],"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\/0000-0002-7954-6246","authenticated-orcid":false,"given":"Olga","family":"Chervyakova","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":"Turyskeldi","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 \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8224-8047","authenticated-orcid":false,"given":"Zhanat","family":"Kondibayeva","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\/0000-0003-3166-4515","authenticated-orcid":false,"given":"Dariya","family":"Toktyrova","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\/0009-0002-3892-0032","authenticated-orcid":false,"given":"Dana","family":"Mazbayeva","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerbol","family":"Bulatov","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Safety Problems, National Holding \u201cQazBioPharm\u201d, Gvardeiskiy 080409, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","first-page":"233","article-title":"Brucellosis in humans\u2014Etiology, diagnostics, clinical forms","volume":"20","year":"2013","journal-title":"Ann. 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