Together with international companies and scientists, Dirk Martens from Wageningen University & Research is involved in the worldwide development of high-performing vaccines against COVID-19. His team's approach however is different compared to many other players in the market. In this interview, Dirk provides some insights about the project scope and why they use the in-line cell density sensor, Incyte, from Hamilton.

Dirk Martens is associate professor for animal cell biotechnology in the bioprocess engineering group of Wageningen University, The Netherlands. Dirk and his team work on process development for the production of pharmaceutical proteins and vaccines using CHO cells and the baculovirus expression system. Within this, his research focus is on modelling the interactions between the cells and the bioreactor environment.
"With Incyte we can detect the right moment when to add the virus to the cell culture and when to harvest."

What are your thoughts on the current developments in the fight against Covid-19?

I think it is going incredibly fast. The first RNA- and vector-based vaccines are on the market now and seem very promising in terms of performance.

How would you describe your project? How does the approach of the consortium you are part of differ from others?

The vaccines that are currently approved and available are based on the expression of the protein in the vaccinated person. The difference in the approach of the consortium we are involved in is that the spike protein itself is produced in bioreactors and next bound to a virus-like particle. When antigens like the spike protein are presented to the immune system bound on a particle, this typically results in a better immune response.

What does your research project look like?

At the laboratory of virology different baculovirus constructs containing the gene for the spike protein are made. Here at bioprocess engineering, we grow insect cells in bioreactors and infect these with the baculovirus constructs to produce the spike protein. Our adjacent laboratory of biochemistry then finally purifies the spike protein.

What are the main challenges you are facing in relation to controlling cell growth?

Our main challenge lies in determining three parameters that interact with each other: the amount of virus that should be added per viable cell (MOI), the ideal cell density to add the virus to the cell culture and finally the optimal time of harvest.

What do you expect from the use of an Incyte sensor in relation to keep the process under control?

The Incyte sensor continuously measures the viable biomass concentration in our bioreactor. This enables us to add the virus at exactly the right moment and possibly we can also determine the right harvest moment based on the probe.

What are the next steps?

Next steps would be to discriminate infected from non-infected cells allowing us to determine the status of the infection/production process and if necessary steer the process in the right direction. In addition further optimization of product yield using some kind of cell concentration based nutrient feeding would be an option.

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