Thanks to a clever modification of the baculovirus, vaccines can now be produced in insect cells more easily and cleaner. Researchers at Wageningen University & Research (WUR) have successfully developed vaccine material without baculovirus contaminants. The method works for different types of vaccines and is compatible with existing production techniques. As a result, vaccines can now be made faster and more cheaply.
Vaccines protect us against dangerous viruses such as the West Nile virus and the tropical chikungunya virus. A widely used method to produce such vaccines is by using so-called virus-like particles, or VLPs. These particles resemble real viruses but contain no genetic material, therefore they cannot replicate. They are safe and still trigger a strong immune response. That is why VLPs are increasingly used in modern vaccines for both humans and animals. A well-known example is the vaccine against the human papillomavirus (HPV), a virus that can cause cervical cancer. A single dose of the vaccine offers long-term protection.
Contamination is a major issue
To produce VLPs, scientists often use insect cells combined with a baculovirus. This virus, which naturally occurs in insects, is used in the lab to instruct cells to produce specific proteins for vaccines. But there's a problem: in addition to the desired VLPs, the cells also produce large quantities of baculovirus particles. These particles are so similar in size and shape to the VLPs that they are extremely difficult to remove from the final product.
This contamination has posed a significant challenge to researchers for years. It makes vaccine production more complex, expensive, and less reproducible. Purifying the VLPs takes time and money, and may affect the vaccine's quality.
Solution through a smart on/off switch
Researchers have now developed a new method to solve this issue, known as the BacFreets technology. This modified version of the baculovirus contains a built-in temperature-sensitive on/off switch. The concept is as simple as it is clever: at 27 degrees Celsius, the baculovirus functions normally. But at a slightly higher temperature of 33 degrees, the baculovirus stops producing its own particles - while VLP production continues unaffected.
By smartly regulating the temperature in the bioreactor, baculovirus contamination in the end product can be almost entirely prevented. According to the researchers, contamination is reduced by up to 99.97%. "We never expected the reduction in baculovirus contamination to be this strong," says former PhD candidate and lead author Dr Linda van Oosten.
Easy to implement
One major advantage of BacFreets is that it fits into existing production methods. The modified viruses can be used with the insect cells and techniques already available in many labs and biotech companies. No costly or complex changes are needed.
The technique has already been tested for VLPs from four different viruses:
- West Nile virus: transmitted by mosquitoes
- Chikungunya virus: found in tropical region
- Coxsackievirus A6: can cause rash and fever
- Foot-and-mouth disease virus: an important virus in livestock
For two of the four viruses (chikungunya and coxsackievirus A6), there was a slight drop in yield at higher temperatures. Even so, the overall result is positive: the strong reduction in contamination makes BacFreets a promising step forward.
Scaling up production
The system already works well in the lab and has achieved a Technology Readiness Level of 4 (TRL4), meaning it has been tested in controlled conditions. The next step is to scale up to industrial production. For this, precise temperature control in the bioreactor is essential. Even a single degree difference can lead to contamination or lower yields.
Purification of the final product will also remain important. Although BacFreets significantly reduces the number of unwanted baculovirus particles, purification steps are still required to produce high-quality clinical vaccines.
Cheaper and faster vaccine production
BacFreets marks an important step towards more efficient and cleaner vaccine production. The method not only helps create better VLP-based vaccines but could also pave the way for cheaper and faster manufacturing processes. This is highly valuable for public health, especially during outbreaks of new viruses, where rapid response and consistent vaccine quality are crucial.
Patent application
Wageningen University & Research has applied for a patent on the BacFreets technology. Interested companies can negotiate licensing agreements to use the method. Any proceeds will be used to support future research at WUR.
Van Oosten reflects positively: "The results are encouraging and pave the way for cleaner vaccine production. The collaboration between virology, process engineering and industry was also extremely valuable."
The research results were published in the scientific journal Trends in Biotechnology.
