Аннотация
Efficient in vitro production of rabies virus is essential for vaccine development and quality control applications. High-density cultivation systems offer practical advantages for rabies virus production but also create culture conditions in which nutrient depletion, waste accumulation, and progressive deterioration of host-cell condition may limit infectious virus output. In this study, we evaluated the effects of sodium pyruvate supplementation on rabies virus CVS-11 production in Vero and BSR cells cultivated in a high-density macrocarrier-based tide-motion culture system under serum-containing and serum-free conditions, with complementary comparative observations in conventional monolayer cultures of BHK cells. Cultures were infected at a multiplicity of infection of 0.01, and infectious virus production was assessed over time, together with cell density, glucose consumption, and pH dynamics. Sodium pyruvate supplementation was associated with significantly higher infectious virus titers, delayed culture deterioration, prolonged maintenance of viable cell populations, and higher peak infectious titers in both Vero and BSR cultures. The highest infectious titers were observed under serum-free pyruvate-supplemented conditions, reaching 7.5 log10 FFU/mL in Vero cells and 7.2 log10 FFU/mL in BSR cells. Across the tested conditions, serum-free cultivation and pyruvate supplementation were both associated with significantly higher peak infectious titers. In contrast, exploratory correlation analysis based on condition-level summary values indicated an inverse association between minimum culture pH and peak infectious titer. Together, these findings show that sodium pyruvate supplementation can improve infectious rabies virus yield and prolong the productive phase in high-density macrocarrier-based cultures, supporting its use as a practical culture-modulation strategy for CVS-11 production in adherent cell systems.