Rise of the Insects: Thermo Fisher Hails Non-Mammalian Expression for Vaccines

Encouraged by success of Flublok and Cervarix, Thermo Fisher says insect protein expression systems are one of the most promising technologies being used in the development of next-generation vaccines.

Thermo Fisher has launched the Gibco ExpiSf system, an insect protein expression system aimed at generating baculovirus using a suspension-based transfection protocol it says delivers protein in half the time compared to traditional insect platforms.

BioProcess Insider spoke with Amy Butler (AB), vice president and general manager, Cell Biology at Thermo Fisher Scientific, about the platform and why such technology could revolutionize vaccine production.

What are the benefits of using insect protein expression systems in vaccine manufacturing, rather than say mammalian cell lines?

AB: Insect systems are easy and fast to implement, easy to scale-up, and more cost-effective than mammalian systems. Insect cells are a suitable host for the production of virus like particles (VLP)-based vaccines, which are one of the most promising recombinant vaccine technologies currently being used for the development of the next-generation of vaccine candidates.

VLPs are highly immunogenic nanoparticles that display the antigen epitopes on their surface yet are non-infectious because they don’t contain viral genetic material. There are a large number of VLP-based vaccine candidates produced in insect cells currently in development.

Why are insect systems not commonly used in bioproduction?

AB: Scientists discovered many years ago that insect cells, particularly from certain moth caterpillars, are particularly good at producing recombinant proteins, or vaccine molecules, when the cells are grown in liquid cultures in the lab. The technologies used to produce protein using insect cells however, have not advanced significantly in the ensuing years.

Is the use in insect-based systems on the up, and is so why?

AB: Although mammalian cell-based expression technologies are most commonly used, the use of insect cells as a production platform for vaccines and biotherapeutics is increasing – particularly after the approval of recombinant vaccines made in insect cells such as Cervarix in 2009, Provenge in 2010 and the influenza vaccine Flublok in 2014.

Several dozens vaccines and gene therapy treatments made in insect cells are in the pre-clinical and clinical development pipeline. Currently there are four insect cell-generated products approved for human use and five for use in animals.

What problems still exist in insect-based platforms, and how does Thermo Fisher’s offering help overcome this?

AB: A key advancement that this field is seeking is the ability to generate large quantities of proteins in a consistent and reliable way.

ExpiSf fills this gap by offering just that: higher proteins yields with a chemically defined medium that supports greater batch-to-batch reproducibility.

Researchers at Thermo Fisher Scientific took a fresh look at these insect cell systems and designed improved methods to grow the cells to higher concentrations in order to produce much more recombinant protein per culture flask or bioreactor. In addition, they were able to remove the variable yeast extracts that have been required to help the cells grow in the lab and replace them with fully defined chemical formulations consisting of amino acids, sugars, vitamins, salts etc. to make the process of protein production much more consistent and reliable.

And how does the ExpiSf system work?

AB: Our technology works by using Sf9 insect cells along with a specialized culture medium and reagents to produce recombinant proteins and virus particles. Basically, you culture insect cells in a vessel, introduce a piece of DNA containing your gene of interest, then your protein/virus of interest is produced by the cells.

Our technology is unique in that it takes advantage of high-density Sf9 cell culture and a chemically defined culture medium formulation as part of a fully-integrated platform where all components work in concert to deliver high performance (i.e., lots of protein).

Read about large-scale, insect cell-based vaccine development in this piece from BioProcess International.