Suspended cell lines for inactivated virus vaccine production

ABSTRACT

Introduction

Inactivated virus vaccines are the most widely used tool to prevent disease. To meet vaccine production demands, increasing attention has been placed on identifying methods to improve vaccine production efficiency. The use of suspended cells can greatly increase vaccine production. Suspension acclimation is a traditional method to convert adherent cells to suspension strains. Furthermore, as genetic engineering technology has developed, increasing attention has focused on the development of suspension cell lines using targeted genetic engineering techniques.

Areas covered

This review systematically summarizes and analyzes the development and research progress of various inactivated viral vaccine production suspension cell lines and provides protocols and candidate target genes for the engineered establishment of additional suspension cell lines for vaccine production.

Expert opinion

The use of suspended cells can significantly improve the production efficiency of inactivated virus vaccines and other biological products. Presently, cell suspension culture is the key component to improve many vaccine production processes.

KEYWORDS:

• Inactivated virus vaccine
• Suspension cell
• Suspension domestication
• Target gene
• Genetic engineering methods
• Siat7e
• Cell adhesion

Article highlights

• Inactivated virus vaccines are the most widely used tool to prevent disease.

• serum-free suspension cell cultures are more suitable for bioreactor-based production processes, which enable large-scale cell culture and a more stable and controlled vaccine production process and improve the process stability of the vaccine.

• The strategy of low serum adaptation to serum-free suspension culture is the simplest and most direct method to domesticate adherent cells into suspension cells.

• Suspension cells can greatly improve the vaccine production efficiency, and many cell lines have been adapted to suspension culture and applied to the production of various virus vaccines, such as COVI-VAC, Newcastle disease, poliovirus, rabies, Foot-and-Mouth disease virus.

• With the discovery of gene editing technology, attention has increasingly been given to functional gene expression modifications in cells to change cell traits.

• For adherent cells, there are a variety of adhesion molecules between the cells and the extracellular matrix (ECM), which enable cells to have the function of adherent growth. If the expression and function of these adhesion molecules are inhibited, the cell adhesion process will theoretically be effectively inhibited, allowing the cell to grow easily in suspension.

• To systematically organize cell adhesion-related studies and propose 11 potential target genes for cell suspension for the first time, which can provide a new idea for the establishment of suspension cells for vaccine production.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors contributed to the article and approved the submitted version. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This research was funded and supported by the National Natural Science Foundation of China (32160164) and National major scientific and technological special project for Significant New Drugs Development (2015ZX09102016).