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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| Format: | Article |
| Language: | English |
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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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| _version_ | 1850137052775972864 |
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| author | Shannon Haughney Seth Clark Elizabeth Carey Nelson Lee Afanador Victoria Stabile Bernard Kang Samantha Marrone Jillian Shingler Carl Hofmann Christopher J. Wang Christopher Ton |
| author_facet | Shannon Haughney Seth Clark Elizabeth Carey Nelson Lee Afanador Victoria Stabile Bernard Kang Samantha Marrone Jillian Shingler Carl Hofmann Christopher J. Wang Christopher Ton |
| author_sort | Shannon Haughney |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-564ad35319a244e0a3a20d7dc2d7c8a2 |
| institution | OA Journals |
| issn | 2590-1362 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Vaccine: X |
| spelling | doaj-art-564ad35319a244e0a3a20d7dc2d7c8a22025-08-20T02:30:58ZengElsevierVaccine: X2590-13622025-06-012410065810.1016/j.jvacx.2025.100658Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriersShannon Haughney0Seth Clark1Elizabeth Carey2Nelson Lee Afanador3Victoria Stabile4Bernard Kang5Samantha Marrone6Jillian Shingler7Carl Hofmann8Christopher J. Wang9Christopher Ton10Bioprocess Drug Substance Commercialization, Merck & Co., Inc., Rahway, NJ, USABiostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, NJ, USAProcess Research & Development, Merck & Co., Inc., Rahway, NJ, USABiostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, NJ, USAProcess Research & Development, Merck & Co., Inc., Rahway, NJ, USAProcess Research & Development, Merck & Co., Inc., Rahway, NJ, USAProcess Research & Development, Merck & Co., Inc., Rahway, NJ, USAProcess Research & Development, Merck & Co., Inc., Rahway, NJ, USAAnalytical Research & Development, Merck & Co., Inc., Rahway, NJ, USAAnalytical Research & Development, Merck & Co., Inc., Rahway, NJ, USAProcess Research & Development, Merck & Co., Inc., Rahway, NJ, USA; Corresponding author.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).http://www.sciencedirect.com/science/article/pii/S259013622500052X |
| spellingShingle | Shannon Haughney Seth Clark Elizabeth Carey Nelson Lee Afanador Victoria Stabile Bernard Kang Samantha Marrone Jillian Shingler Carl Hofmann Christopher J. Wang Christopher Ton Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers Vaccine: X |
| title | Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers |
| title_full | Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers |
| title_fullStr | Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers |
| title_full_unstemmed | Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers |
| title_short | Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers |
| title_sort | optimization for the production of a dengue live attenuated quadrivalent vaccine in vero cells grown on microcarriers |
| url | http://www.sciencedirect.com/science/article/pii/S259013622500052X |
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