Enhanced production of yellow fever virus through tailored culture media optimization

Abstract

In the present study, an initial screening was conducted using 12 types of cell culture media, and four media with the best performance were selected for further study. The optimization of four media blend for YFV production was evaluated using an Augmented simplex centroid mixture design. Among all the different models that were investigated, the quadratic model was found to be the most appropriate model for exploring mixture design. It was found that M10 exhibited the greatest impact on YFV production, followed by M9, M4, and M1. The utilization of M1 and M4 media individually yielded higher compared to their blends with other media. The YFV titers were reduced when M1 media was combined with other media. The utilization of M9 and M10 media in combination resulted a higher viral yield compared to their respective concentrations. The optimal ratio for achieving a higher titer of YFV from primary CEFs was found to be approximately 38:62, with M9 and M10 being the most favorable media blend. The use of a media mixture led to a significant increase of virus titer up to 2.6 × 10⁸ PFU/ml or 2 log titer yield, which is equivalent to 1.92 × 10⁵ doses, without any changes to growth conditions or other process factors. This study concluded that the utilization of a mixture design could be efficiently employed to choose the optimal combination of media blends for enhanced viral production from cell culture.

Keywords:

• Cell culture
• chicken embryonic fibroblasts
• media blend
• mixture design
• yellow fever vaccine
• yellow fever virus

Acknowledgements

The authors express their gratitude to Biological E Ltd for generously providing the lab facility to conduct the study.

Disclosure statement

No conflict of interest was reported by the authors.