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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Bibliographic Details
Main Authors: Shannon Haughney, Seth Clark, Elizabeth Carey, Nelson Lee Afanador, Victoria Stabile, Bernard Kang, Samantha Marrone, Jillian Shingler, Carl Hofmann, Christopher J. Wang, Christopher Ton
Format: Article
Language:English
Published: Elsevier 2025-06-01
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).
ISSN:2590-1362