Virus Like Particle (VLP)
VLPs are small particles that contain multiprotein components which can be an envelope or capsid from the outer coating of a virus. Virus like particles (VLPs), however, doesn’t contain any infectious genome that a real virus have. It is for this reason that VLPs can be a very valuable tool in several applications like gene therapy, nanotechnology and diagnostics, and vaccination.
Studies have shown that since VLPs’ mimic the same morphology of a native virus without its viral genome it can also be a good candidate as vectors for gene transfer. Its non-replicating property makes it a very viable tool to deliver foreign plasmid DNA. Several studies on the use of VLP as a gene delivery system have shown positive results but validation and further clinical trials has to be performed yet before it becomes available in the market.
Nanotechnology and Diagnostics
During the viral life cycle, a virus transports its genome to a host cell. Hence, the use of a virus can be one of the most efficient and practical way to deliver nanoparticles based drugs as well as diagnostic agents since viruses can be considered as natural nanocarriers. However, the use of virus as delivery system imposes high risk of viral production. It is for this reason that VLPs can be used as a very viable delivery system due to its likelihood to a virus only without the infectious genome in it.
Since VLPs, just like native virus, can also be considered as natural nanocarriers its potential of producing safe and cost effective vaccines is greatly explored. Currently, several VLP based vaccine manufactured by big pharmaceutical manufacturing companies are already available in the market. Some of these vaccines already available in the market are Hepatitis B Virus vaccine and Human Papilloma Virus vaccine. Also, several VLP-based vaccine, for the treatment of influenza, parvovirus, and Norwalk, are currently undergoing clinical trials and are expected to hit the market in the next few years.
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
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.
Baculovirus Insect cell lines
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.
Plant cell lines
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.
Mammalian cell lines
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.
What VacciXcell Offers
VacciXcell offers different types of bioreactors, suited for various types of cells and applications. For adherent cell types, VacciXcell offers Tide Motion System which is the main bioprocessing principle of Celcradle® and Tidecell®, has the following advantages including high cell yield, high product yield, extremely low shear stress, zero bubbling and foaming, efficient medium consumption, lower space and labor requirements and reduced downstream bioprocessing costs. CelCradle™ is the labscale disposable bioreactor capable of high density cell culture for protein expression, virus and monoclonal antibody production. It is designed based on the concept of bellow-induced intermittent flow of media and air through porous matrices, where cells reside. This provides a extremely low shear, high aeration, and foam-free culture environment. Tidecell®, on the other hand, is the extended large scale system of the lab scale CelCradle® bioreactor system. In this system, a matrix vessel is packed with porous BioNoc™ II carriers and functions as an artificial lung with huge contact surface for nutrition and aeration. It also has a 10 fold higher cell yield than growing in suspension as new media can be refreshed after cell growth to infect virus with completely new media. Unlike any other stirred tank or packed bed bioreactor system, Tidecell can do 100% media refreshment while on perfusion mode. As a result, bioprocessing time and costs are greatly reduced. VacciXcell's bioreactors also boast of its true linear scalability platform where production scale up is as easy as adding equipment but the bioprocessing principles are the same.
Currently, production of VLPs are usually done using a stirred tank bioreactor in batch, fed batch or perfusion mode. VacciXcell completes its bioprocessing solutions by providing a system for the fermentation of microorganisms and culture of suspension cells – StirCradle™ and StirCradle™-Pro. The StirCradle is the laboratory-scale autoclavable system while the StirCradle-Pro is the SIP pilot/production scale system. VacciXcell offers a wide range of fermenter sizes, starting from 5L laboratory scale all the way to 2000L production scale. Also, the cells' surrounding conditions greatly affect their growth and development whether in vivo or in vitro, with culture medium being a key aspect in the latter setup; therefore the choice of a culture medium is vital to the success of cell culture experiments. Hence, VacciXcell offers various cell culture media in order to suit your cells’ specific needs. All of VacciXcell’s fementers, bioreactors, and culture medium are designed and formulated to deliver optimum performance at minimum cost. This is in line with our vision to deliver bioprocessing solutions to address everyone’s bioprocessing needs.