BIOREACTOR TECHNOLOGY OF SUSPENSION CULTIVATION OF THE RABIES VIRUS CVS-11

Abstract

The development of bioreactor technologies of suspension cultivation is a promising tool for producing large quantities of cells for subsequent virus infection.
Traditional static cultivation methods using flasks are widely employed but present several significant drawbacks.
These include high risks of fungal and bacterial contamination, low virus yield against large cultivation area requirements, and complex technological workflows.
Modern bioreactor cultivation technologies address these limitations while offering substantial advantages, including automated control of key parameters such as temperature, pH, and dissolved oxygen levels. Additionally, bioreactors enhance production scalability, improve process oversight, and reduce costs. The study employed virological and biotechnological methods to adapt BHK-21 cell culture, followed by its cultivation in a bioreactor and the assessment of the concentration of the rabies virus CVS-11.
The results demonstrated that BHK-21 cells adapted well to suspension conditions, showing a gradual reduction in cell aggregates and an increase in cell density to 2.11±0.11×10⁶ cells/cm³. The proposed suspension cultivation method achieved a high rabies virus titer of 7.25 lg TCD50/cm³, equivalent to 30-40 million viral particles per 1 cm³. In contrast, in case of static cultivation method using flasks, the biological activity titer reached 6.5 lg TCD50/cm³, which, when converted via the antilogarithm, equates to 3–4 million viral particles per 1 cm³.
The findings highlight the potential of suspension ultivation as a modern tool for industrial production of rabies vaccines and diagnostic test kits. This technology represents a significant step forward in improving the efficiency and safety of rabies vaccine production, with the potential to significantly reduce rabies incidence in humans and animals.