A baculovirus expression system free of contaminating baculovirus particles (BACFREE)
The BACFREE project aims to develop a baculovirus expression system that allows the production of pharmaceuticals free of contaminating baculovirus particles.
The baculovirus expression vector system (BEVS) is a widely used technology to produce vaccines and viral vectors for gene therapy. Insect cells are infected with a baculovirus containing the gene of interest and next produce the target protein. The strength of this expression system lies in its ability to produce relatively large quantities of recombinant protein in a short amount of time. This is very useful when a quick response to urgent disease outbreaks, such as Zika and Ebola, and more recently COVID-19, is needed.
However, the BEVS is also characterized by co-production of progeny baculovirus particles. For some vaccine products, e.g. certain virus like particle vaccines, these baculovirus particles resemble the product. This makes separation difficult and consequently often valuable product is lost during downstream processing. In bioprocess engineering (BPE) we perform experiments in bioreactors (see picture) to optimize product yield and minimize the presence of baculovirus particles. These bioreactors resemble the conditions at large scale and allow us to evaluate the optimal protein production strategies using this system.
In collaboration with the Laboratory of Virology (VIR), different molecular and process strategies are being developed such that the target protein will be expressed while the formation of baculovirus particles is blocked. At BPE we test these strategies in bioreactors and asses their suitability for scale-up and large scale protein production. In addition, we develop models and apply novel methods such as online monitoring and screening microbioreactors to increase our understanding of the process.