Sharing Knowledge: Expressing in a Baculovirus System

Baculovirus Expression Vector Systems are well suited for the production of Virus Like Particles, which have excellent properties for vaccine applications

Microbiology, microscopic image, virus-like structure. Abstract planet.3d illustration

Baculovirus Expression Vector systems are capable of producing proteins that are very large in size.

These systems are also capable of producing multiprotein subunit complexes such as Virus Like Particles (VLPs) which are known to induce broad and strong immune responses, making them ideal in vaccine production. Other advantages of using a Baculovirus system is that they can modify proteins post translationally, e.g., phosphorylation and glycosylation.

Transmission Electron Microscopy of a Baculovirus

Colour enhanced transmission electron micrograph (TEM) of a Baculovirus.

It is important to note that the post translational modifications are usually not to the the same extent as higher eukaryotes such as CHO. Baculovirus can produce product intracellularly or extracellularly-excreted.

Insect cell culture is relatively inexpensive to produce as they typically do not require expensive feeds or additives.

Typical cells used in insect cell culture, sf21 and Sf9 which are ovarian cells from the fall army worm- Spodoptera frugiperda, can interestingly be grown either attached or suspended.

What are particular challenges of working with Baculovirus Systems?

There are a few challenges when working with BEVS that should be kept in mind. BEVS are not able to fully glycosylate proteins so they are not a suitable system for the expression of  antibodies.

From an Upstream Development perspective,  media selection is an area that must be carefully considered as in our experience chemically defined medias do not work well in Insect Cell cultures. Purification can be a challenge mainly due to the low expression levels achieved by BEVS, especially when there is a capture step in the purification scheme.  Purification of BEVS can go through very drastic scale changes, starting as very large processes going to become very low volume within a few units of operations. Having a solid and experience Downstream Development team is very important when working with BEVS.

The use of BEVS as an expression systems is still mainly academic. This may make Process Development a little more of an adventure as production optimization information in a large scale and/or cGMP setting is usually minimal.

What do we bring to your program?

We bring over 15 years of hand-on baculovirus experience to your program. We have deep understanding of the challenges that will make a baculovirus program successful, not only in development but taking all to the way to cGMP production, executing validation campaign(s) and supporting BLA and subsequent commercialization.

We are a licensed manufacturer of a commercially approved baculovirus expressed product.

How do we help?

With extensive Baculovirus  development and manufacturing experience and a  team of expert scientists, FUJIFILM Diosynth Biotechnologies offers a full range of process and analytical development services, combined with flexible cGMP manufacturing assets, to support you through the full life cycle of your product, from development to clinical and commercial manufacture.