date: 2024-07-09T08:03:33Z
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pdf:docinfo:title: Parallel Multifactorial Process Optimization and Intensification for High-Yield Production of Live YF17D-Vectored Zika Vaccine
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Keywords: live-attenuated vaccine; process intensification; virus yield; high cell density; suspension cells; YF17D; Zika vaccine
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subject: The live-attenuated yellow fever 17D strain is a potent vaccine and viral vector. Its manufacture is based on embryonated chicken eggs or adherent Vero cells. Both processes are unsuitable for rapid and scalable supply. Here, we introduce a high-throughput workflow to identify suspension cells that are fit for the high-yield production of live YF17D-based vaccines in an intensified upstream process. The use of an automated parallel ambr15 microbioreactor system for screening and process optimization has led to the identification of two promising cell lines (AGE1.CR.pIX and HEKDyn) and the establishment of optimized production conditions, which have resulted in a >100-fold increase in virus titers compared to the current state of the art using adherent Vero cells. The process can readily be scaled up from the microbioreactor scale (15 mL) to 1 L stirred tank bioreactors. The viruses produced are genetically stable and maintain their favorable safety and immunogenicity profile, as demonstrated by the absence of neurovirulence in suckling BALB/c mice and consistent seroprotection in AG129 mice. In conclusion, the presented workflow allows for the rapid establishment of a robust, scalable, and high-yield process for the production of live-attenuated orthoflavivirus vaccines, which outperforms current standards. The approach described here can serve as a model for the development of scalable processes and the optimization of yields for other virus-based vaccines that face challenges in meeting growing demands.
dc:creator: Sven Göbel, Ozeir Kazemi, Ji Ma, Ingo Jordan, Volker Sandig, Jasmine Paulissen, Winnie Kerstens, Hendrik Jan Thibaut, Udo Reichl, Kai Dallmeier and Yvonne Genzel
dcterms:created: 2024-07-09T07:45:18Z
Last-Modified: 2024-07-09T08:03:33Z
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title: Parallel Multifactorial Process Optimization and Intensification for High-Yield Production of Live YF17D-Vectored Zika Vaccine
Last-Save-Date: 2024-07-09T08:03:33Z
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pdf:docinfo:keywords: live-attenuated vaccine; process intensification; virus yield; high cell density; suspension cells; YF17D; Zika vaccine
pdf:docinfo:modified: 2024-07-09T08:03:33Z
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dc:title: Parallel Multifactorial Process Optimization and Intensification for High-Yield Production of Live YF17D-Vectored Zika Vaccine
modified: 2024-07-09T08:03:33Z
cp:subject: The live-attenuated yellow fever 17D strain is a potent vaccine and viral vector. Its manufacture is based on embryonated chicken eggs or adherent Vero cells. Both processes are unsuitable for rapid and scalable supply. Here, we introduce a high-throughput workflow to identify suspension cells that are fit for the high-yield production of live YF17D-based vaccines in an intensified upstream process. The use of an automated parallel ambr15 microbioreactor system for screening and process optimization has led to the identification of two promising cell lines (AGE1.CR.pIX and HEKDyn) and the establishment of optimized production conditions, which have resulted in a >100-fold increase in virus titers compared to the current state of the art using adherent Vero cells. The process can readily be scaled up from the microbioreactor scale (15 mL) to 1 L stirred tank bioreactors. The viruses produced are genetically stable and maintain their favorable safety and immunogenicity profile, as demonstrated by the absence of neurovirulence in suckling BALB/c mice and consistent seroprotection in AG129 mice. In conclusion, the presented workflow allows for the rapid establishment of a robust, scalable, and high-yield process for the production of live-attenuated orthoflavivirus vaccines, which outperforms current standards. The approach described here can serve as a model for the development of scalable processes and the optimization of yields for other virus-based vaccines that face challenges in meeting growing demands.
pdf:docinfo:subject: The live-attenuated yellow fever 17D strain is a potent vaccine and viral vector. Its manufacture is based on embryonated chicken eggs or adherent Vero cells. Both processes are unsuitable for rapid and scalable supply. Here, we introduce a high-throughput workflow to identify suspension cells that are fit for the high-yield production of live YF17D-based vaccines in an intensified upstream process. The use of an automated parallel ambr15 microbioreactor system for screening and process optimization has led to the identification of two promising cell lines (AGE1.CR.pIX and HEKDyn) and the establishment of optimized production conditions, which have resulted in a >100-fold increase in virus titers compared to the current state of the art using adherent Vero cells. The process can readily be scaled up from the microbioreactor scale (15 mL) to 1 L stirred tank bioreactors. The viruses produced are genetically stable and maintain their favorable safety and immunogenicity profile, as demonstrated by the absence of neurovirulence in suckling BALB/c mice and consistent seroprotection in AG129 mice. In conclusion, the presented workflow allows for the rapid establishment of a robust, scalable, and high-yield process for the production of live-attenuated orthoflavivirus vaccines, which outperforms current standards. The approach described here can serve as a model for the development of scalable processes and the optimization of yields for other virus-based vaccines that face challenges in meeting growing demands.
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pdf:docinfo:creator: Sven Göbel, Ozeir Kazemi, Ji Ma, Ingo Jordan, Volker Sandig, Jasmine Paulissen, Winnie Kerstens, Hendrik Jan Thibaut, Udo Reichl, Kai Dallmeier and Yvonne Genzel
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creator: Sven Göbel, Ozeir Kazemi, Ji Ma, Ingo Jordan, Volker Sandig, Jasmine Paulissen, Winnie Kerstens, Hendrik Jan Thibaut, Udo Reichl, Kai Dallmeier and Yvonne Genzel
meta:author: Sven Göbel, Ozeir Kazemi, Ji Ma, Ingo Jordan, Volker Sandig, Jasmine Paulissen, Winnie Kerstens, Hendrik Jan Thibaut, Udo Reichl, Kai Dallmeier and Yvonne Genzel
dc:subject: live-attenuated vaccine; process intensification; virus yield; high cell density; suspension cells; YF17D; Zika vaccine
meta:creation-date: 2024-07-09T07:45:18Z
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meta:keyword: live-attenuated vaccine; process intensification; virus yield; high cell density; suspension cells; YF17D; Zika vaccine
Author: Sven Göbel, Ozeir Kazemi, Ji Ma, Ingo Jordan, Volker Sandig, Jasmine Paulissen, Winnie Kerstens, Hendrik Jan Thibaut, Udo Reichl, Kai Dallmeier and Yvonne Genzel
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