Hypersecretion of OmlA antigen in Corynebacterium glutamicum through high-throughput based development process

Area of Science:

• Biotechnology
• Vaccine Development
• Microbial Fermentation

Background:

• Porcine contagious pleuropneumonia (PCP) significantly impacts the swine industry.
• Outer membrane lipoprotein A (OmlA) is a key vaccine antigen for PCP.
• Developing efficient production methods for OmlA is crucial for disease control.

Purpose of the Study:

• To systematically enhance the secretory production of OmlA in Corynebacterium glutamicum.
• To establish a holistic development process for high-yield recombinant vaccine production.
• To achieve a high yield of OmlA for potential vaccine applications.

Main Methods:

• Utilized a high-throughput culture platform for screening and optimization.
• Optimized expression elements, medium composition, and induction conditions in microwell plates.
• Performed fermentation parameter optimization using a 4x1 L parallel fermentation system (CUBER4) and scaled up to a 5-L bioreactor.

Main Results:

• Achieved an unprecedented yield of 1.01 g/L of OmlA.
• Successfully scaled up production using a fixed oxygen mass transfer coefficient (kLa) strategy.
• The produced OmlA antigen demonstrated effective protective immunity against Actinobacillus pleuropneumoniae challenge.

Conclusions:

• Developed a rapid and reliable pipeline for hyper-production of OmlA in C. glutamicum.
• The established process is potentially applicable to other recombinant vaccines.
• This work provides a significant advancement in the biotechnological production of veterinary vaccines.