Virus-like particles (VLPs) can be produced using various cell culture production expression systems including bacteria and yeast cells, insect cell lines, mammalian cell lines and plant cells.
Bacteria and yeast cells production is the simplest expression system which can be applicable for VLPs of no more than two proteins. This cell culture system uses a stirred tank bioreactor to proliferate the VLP-infected bacterial/yeast cells. One limitation of using bacteria/yeast cells expression system is the inability of the bacteria to perform post translational modifications (PTMs) which will make the bioseparation and downstream processing difficult and expensive.
Insect cell lines production expression system is the most commonly used cell culture system due to its simplicity and cost effectiveness. Also, insect cell lines can undergo simple post translational modifications (PTMs) which makes downstream processing cost less expensive. However, one limitation of this system is that baculovirus is hard to detach from the VLPs thus more laborious downstream processing efforts must be employed.
The primary advantage of using this expression system is the low upstream and downstream processing cost. However, plant cells cannot undergo post translational modifications (PTMs) which results to low protein expression levels. Hence, this system is only applicable for VLPs of not more than one protein.
Among all expression systems the use of mammalian cells offer the most robust cell culture results as it can undergo complex post translational modifications (PTMs) which results to high protein expression levels. This system can also produce single or multilayered VLPs of up to five proteins. The main limitation of the use of mammalian cells, on the other hand, is its relative high upstream and downstream processing cost.