Risk-Based Bioengineering Strategies for Reliable Bacterial Vaccine Production

Tjerko Kamminga, Simen Jan Slagman, Vitor A.P. Martins dos Santos, Jetta J.E. Bijlsma, Peter J. Schaap*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Design of a reliable process for bacterial antigen production requires understanding of and control over critical process parameters. Current methods for process design use extensive screening experiments for determining ranges of critical process parameters yet fail to give clear insights into how they influence antigen potency. To address this gap, we propose to apply constraint-based, genome-scale metabolic models to reduce the need of experimental screening for strain selection and to optimize strains based on model driven iterative Design–Build–Test–Learn (DBTL) cycles. Application of these systematic methods has not only increased the understanding of how metabolic network properties influence antigen potency, but also allows identification of novel critical process parameters that need to be controlled to achieve high process reliability.

Original languageEnglish
Pages (from-to)805-816
JournalTrends in Biotechnology
Volume37
Issue number8
Early online date5 Apr 2019
DOIs
Publication statusPublished - Aug 2019

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Keywords

  • bacterial vaccines
  • constraint-based
  • genome-scale metabolic models
  • process analytical technology
  • risk-based process design

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