Efficient Serum-Free Rabies Virus Propagation Using BSR and Vero Cell Lines: A Comparative Evaluation of BioNOC II® Macrocarriers in the BelloStage™-3000 Bioreactor Versus Conventional Microcarriers
Amanova Z. Sametova Z. Turyskeldy S. Kurmasheva A. Abitayev R. Ussembay A. Kondibaeva Z. Toktyrova D. Mazbayeva D. Nurabayev S. Kerimbayev A. Bulatov Y.
October 2025Multidisciplinary Digital Publishing Institute (MDPI)
Biology
2025#14Issue 10
The rabies virus remains a significant public health threat, particularly in regions with limited access to vaccination. This study shows that the BelloStage™-3000 bioreactor, operating on the “Tide Motion” principle, in combination with BioNOC® II macrocarriers, ensures highly efficient rabies virus cultivation in BSR and Vero cells grown in serum-free OptiPRO™ 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™-3000 bioreactor system with BelloCell™ 500A disposable vials and BioNOC II® 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 × 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 × 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® II macrocarriers, the BelloStage™-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.
bioreactor , BSR cell line , macrocarrier , microcarrier , rabies virus , serum-free culture medium , Vero cell line
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Research Institute for Biological Safety Problems, National Holding “QazBioPharm”, Gvardeiskiy, 080409, Kazakhstan
Research Institute for Biological Safety Problems
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