Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers
Dengue is a mosquito-borne disease and is a major global health threat, especially in tropical and subtropical regions. In this study, we describe the optimization of virus production for a dengue live-attenuated quadrivalent vaccine candidate and demonstrate scalability of a stirred tank bioreactor...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | Vaccine: X |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259013622500052X |
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| Summary: | Dengue is a mosquito-borne disease and is a major global health threat, especially in tropical and subtropical regions. In this study, we describe the optimization of virus production for a dengue live-attenuated quadrivalent vaccine candidate and demonstrate scalability of a stirred tank bioreactor serum-free microcarrier process. We utilized a design-of-experiment (DoE) methodology to optimize for pH and temperature and evaluate effect of Multiplicity of Infection (MOI) and Time of Infection (TOI) for each serotype during virus production in 2 L and 3 L bioreactors. The optimal pH and temperature for dengue virus production achieved ∼10× higher virus titer at peak virus production for all 4 serotypes compared to baseline condition. Different MOI and TOI did not impact peak virus production. Results from the DoE studies were successfully scaled to the 50 L Single-Use Bioreactor (SUB). |
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| ISSN: | 2590-1362 |