Systems analysis of Mycoplasma hyopneumoniae to improve vaccine production

Abstract

Chapter 1 General introduction 1 Chapter 2 Risk-based bioengineering strategies for reliable bacterial vaccine production Chapter 3 Metabolic modeling of energy balances in Mycoplasma hyopneumoniae shows that pyruvate addition increases growth rate Chapter 4 Reliable production of bacterial vaccines necessitates robust production strains and optimized process controls in a conjoint process to reach optimal antigenic mass yields. While bioengineering techniques have been successfully applied to improve strains for production of biochemicals, rational design and subsequent bioengineering of production strains for bacterial vaccines has been hampered by an incomplete understanding of critical process parameters and a lack of early focus on risk-based process development. Early identification of process risks, captured in a description of critical process parameters, is required for optimal vaccine bioengineering. Here, we propose to use a suite of system metabolic engineering tools, integrated in the vaccine development pipeline, to rationally design production strains and conditions for bacterial vaccines. Model-based understanding of the relation between metabolic flux and production of antigenic mass forms the basis for our approach. In addition, we propose to implement process analytical techniques emanating from model-based interpretation of high-throughput (omics) data to monitor and control the production process. Implementation of this workflow requires collaborative process risk assessments performed by academia and industry at multiple stages in the project.