Mathematical Model for Measles Virus Production in Batch Bioreactors.

Measles virus (MeV) is a promising vector for vaccines, gene therapy, and oncolytic virus therapy due to its safety, efficacy, and natural ability to target tumor cells. However, MeV production in bioreactors, typically with microcarrier cultures of Vero cells, is challenging because of the sensitivity of the virus to temperature, shear stress, and low pH. At 37°C, the optimal growth temperature of Vero cells, MeV has a short half-life of 1 h, requiring precise control of the harvest time (TOH) to maximize yield. We developed a mathematical model to predict the TOH for recombinant MeV production in Vero cells. Model predictions for TOH were in good agreement with observations across five separate bioreactor runs, despite significant run-to-run performance variations. Parameter analysis revealed that virus attachment parameters and thermal degradation rate significantly influence infection dynamics. Furthermore, the model highlights the critical importance of accurately characterizing seed virus quality, particularly concerning defective interfering particle (DIP) content, to minimize production variability and optimize yield.