A fast, efficient, and scalable method for purifying recombinant SARS-CoV-2 spike protein

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Vaccine Development

Background:

• Recombinant SARS-CoV-2 trimeric spike protein is a key COVID-19 vaccine candidate.
• Large-scale production of this protein is hindered by purification challenges using conventional resin-based chromatography due to its size.
• Slow diffusion rates and low binding capacity limit the efficiency of resin-based purification.

Purpose of the Study:

• To develop a fast and scalable membrane chromatography-based purification method for recombinant SARS-CoV-2 trimeric spike protein.
• To address the limitations of traditional purification techniques for large biopharmaceutical proteins.

Main Methods:

• Utilized membrane chromatography, specifically cation exchange laterally-fed membrane chromatography combined with size exclusion chromatography.
• Applied convective solute transport inherent to membrane chromatography for efficient purification of large proteins.
• Processed mammalian cell culture supernatant containing the target protein.

Main Results:

• Achieved a homogeneous spike protein sample using the proposed membrane chromatography method.
• Demonstrated the speed and scalability of the developed purification process.
• Overcame the slow binding kinetics and low capacity issues associated with resin-based chromatography.

Conclusions:

• Membrane chromatography provides an efficient and scalable alternative for purifying large proteins like the SARS-CoV-2 spike protein.
• The developed method is suitable for the fast, large-scale manufacture of vaccine-grade spike protein.
• This approach could significantly advance COVID-19 vaccine production capabilities.