LAUSR

To face the COVID-19 pandemic caused by the SARS-CoV-2 virus, our institute has developed the rVSV-ΔG-spike vaccine, in which the glycoprotein of VSV was replaced by the spike protein of SARS-CoV-2. Many process parameters can influence production yield. To maximize virus vaccine yield, each parameter should be tested independently and in combination with others. Here, we report the optimization of the production of VSV-ΔG-spike vaccine in Vero cells using the Ambr15 system. This system facilitates high-throughput screening of process parameters, as it contains 24 individually controlled, single-use stirred-tank mini-reactors. During optimization, critical parameters were tested. Those parameters included: cell densities; multiplicity of infection (MOI); virus production temperature; medium addition and medium exchange and supplementation of glucose in the virus production step. Virus production temperature, medium addition and medium exchange were all found to significantly influence the yield. The optimized parameters were tested in the BioBLU 5p bioreactors production process and those that were found to contribute to the vaccine yield were integrated in the final process. The findings of this study demonstrate that the Ambr15 system is an effective tool for bioprocess optimization of vaccine production using macro-carriers and that the combination of production temperature, rate of medium addition and medium exchange significantly improved virus yield. This article is protected by copyright. All rights reserved.