Optimization of Virus Yield as a Strategy to Increase the Efficiency of Rabies Vaccine by BHK-21 Cells in a Bioreactor

Abstract

Background: Rabies is a usually fatal viral zoonotic and preventable disease. The efficacy and safety of animal rabies vaccination made in permanent BHK-21 cell culture have been proven over a long period of use. By increasing the yield of cells and viruses, the efficacy of the vaccine can be increased. Objectives: The objective of this study was to optimize and maximize the output of a rabies vaccine made on BHK cells in a bioreactor. Methods: This study examined the impacts of independent parameters, such as pH, temperature, cell density, and dissolved oxygen (DO), on rabies virus strain PV-PARIS yield for a central composite design. To achieve high viral production, this study used the central composite approach to optimize cell development. Results: The findings showed that BHK-21 cells were grown under the ideal conditions of pH 7.21, temperature 35.05ºC, 68.75% for DO, and 2.30 × 106 cell/mL of cell density to produce high titers of rabies virus (4.7 × 107 plaque-forming unit [PFU]/mL). High correlation coefficients (0.927) validated that the predicted model was well-fitted with the data, and the statistical analysis of the collected data indicated that the experimental data and predicted model were well-matched. The accuracy of this model’s predictions was correlated with values of adjusted R-squared (R2Adj) and predicted R-squared (R2Pred). Conclusions: These upgrades lead to a more reliable and economical procedure that makes industrialization and commercialization easier.