Production of a Foot-and-Mouth Disease Vaccine Antigen Using Suspension-Adapted BHK-21 Cells in a Bioreactor
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines, Cell Culture Media, and FMDV
2.2. Suspension Adaptation of Adherent BHK-21 Cells and Maintenance of a BHK-21 Suspension (BHK-S) Culture
2.3. Cell-Adhesion Assay
2.4. Development of Serum-Free Medium for BHK-S Cells
2.5. Propagation and Titration of FMDV
2.6. 146S Antigen Quantification
2.7. Optimizing BHK-S Batch Culture
2.8. Scaled Up FMDV Production in 50 L and 200 L Bioreactors
3. Results
3.1. Suspension Adaptation and BHK-S Cell Growth
3.2. ECM Properties of BHK-S Cells
3.3. FMDV Susceptibility and Productivity of BHK-S Cells
3.4. Developing Serum-Free Medium for BHK-S Cells
3.5. Optimizing BHK-S Batch Culture and Scaled-Up FMDV Production in a Bioreactor
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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VCD at Day 3 (106 cells/cm2 or cells/mL) | Doubling Time (h) | Specific Growth Rate (h−1) | |
---|---|---|---|
BHK-21 (C13) | 0.45 (±0.02) | 15.53 (±0.69) | 0.045 (±0.002) |
BHK-S | 7.65 (±0.71) | 15.97 (±0.57) | 0.043(±0.002) |
Scale-Up | Cell Density at Infection (cells/mL) | Virus Titer (TCID50/mL) | 146S Antigen (μg/mL) |
---|---|---|---|
250 mL Flask | 7.98 (±0.14) | 25.00 (±2.35) | 2.30 (±0.28) |
50 L bioreactor | 10.83 | 9.70 | 2.56 |
200 L bioreactor | 6.58 | 11.00 | 2.10 |
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Park, S.; Kim, J.Y.; Ryu, K.-H.; Kim, A.-Y.; Kim, J.; Ko, Y.-J.; Lee, E.G. Production of a Foot-and-Mouth Disease Vaccine Antigen Using Suspension-Adapted BHK-21 Cells in a Bioreactor. Vaccines 2021, 9, 505. https://doi.org/10.3390/vaccines9050505
Park S, Kim JY, Ryu K-H, Kim A-Y, Kim J, Ko Y-J, Lee EG. Production of a Foot-and-Mouth Disease Vaccine Antigen Using Suspension-Adapted BHK-21 Cells in a Bioreactor. Vaccines. 2021; 9(5):505. https://doi.org/10.3390/vaccines9050505
Chicago/Turabian StylePark, Soonyong, Ji Yul Kim, Kyoung-Hwa Ryu, Ah-Young Kim, Jaemun Kim, Young-Joon Ko, and Eun Gyo Lee. 2021. "Production of a Foot-and-Mouth Disease Vaccine Antigen Using Suspension-Adapted BHK-21 Cells in a Bioreactor" Vaccines 9, no. 5: 505. https://doi.org/10.3390/vaccines9050505