Researchers develop effective vaccine against cow parasite by modifying sugar structures in plants

Mimicking sugary structures in plants plays a crucial role in the development of effective vaccines against the stomachworm Ostertagia ostertagi. This was demonstrated by Ruud Wilbers of Wageningen University and Research (WUR), together with researchers from Ghent University and Leiden University Medical Center, in a validation study. of principle.

Their research shows that a vaccine produced in a plant protects cows against the parasite. The ideas were published in an article in Scientific reports and will provide a springboard for the faster and more sustainable development of parasite vaccines.

Stomachworm infection is a common condition in cows. Infection can lead to reduced milk and meat production and even disease if the parasite load is high. It is for this reason that infected cows are treated with dewormers. But this creates new problems, according to researcher Ruud Wilbers.

“Overuse of these drugs, such as administering them too frequently and at the wrong dose, causes the parasite to develop resistance to the drugs. In the Western world in particular, where much livestock farming is intensive, resistance is a growing problem.”

Additionally, Wilbers continues, deworming does not offer a lasting solution. “This simply ensures that the parasite is eliminated from the animal. But the following year, the infection can return if the cow ingests an egg while eating grass. Since infected cows spread their eggs with each bowel movement, the pastures remain contaminated, keeping the parasite viable.”

Current vaccine production is undesirable

A much more effective and sustainable approach is to vaccinate cows against the parasite. There are currently three vaccines available against parasitic worms, according to Wilbers. “The only problem is that, to produce these vaccines, you have no choice but to infect animals. The antigens are isolated from live parasites. This method is undesirable, mainly because it requires then infect healthy animals. It is also not sustainable if you want to develop vaccines on a large scale. Indeed, you would need a lot of infected cows to get enough vaccine.

An alternative production method uses a recombinant expression system. This involves inserting the DNA genetic code of a parasite antigen into another organism, such as yeast or bacteria. Wilbers says: “This process produces the antigen needed for vaccine development. The only problem with this method is that it does not work against stomach worms. Researchers at Ghent University spent a decade trying to identify the right antigen. But they discovered that it no longer works if you make it with yeast. This is because other organisms cannot reconstruct the parasite’s natural sugar (glycan) structures.

At a conference in Greece, Wilbers came into contact with researchers from Ghent and discovered the problem they were facing. “I was there for a presentation on making worm proteins in our plant expression system. We teamed up and began researching how to mimic the parasite protein in plants. Initially, in collaboration with LUMC, We looked at the sugar composition of the parasite and how similar it was to that of plants. In stomach worms, the glycans are not very complex compared to other parasitic worms. We determined what sugar residues are on them and what enzymes are needed to make them.

A plant’s main advantage over other expression systems is that it has very few enzymes to manipulate sugars, Wilbers says. “This makes it easy to remove existing sugar structures and start with a ‘bare’ structure. From there you build a new structure, so to speak, by placing sugar cubes on top with your chosen enzymes. C It’s a bit like Lego.” For experts. Plants also tolerate this modification. We then allow the enzymes of the new structure to be expressed in the plant at the same time as the antigen. ”

Proof-of-concept study shows vaccine effectiveness

Through a proof-of-concept study, the researchers showed that sugar composition is indeed crucial for vaccine effectiveness. “This discovery is at the center of the article by Scientific reports. Previous research suggested this, but conclusive evidence was lacking. This discovery will serve as a springboard for the development of vaccines against other livestock parasites, such as the liver fluke, as well as against human parasites. We will now carry out several projects to further explore the potential. Mimicking sugar structures in plants is expected to accelerate the development of vaccines against parasitic worms. »

In the future, Wilbers hopes to be able to completely separate sugars from proteins. “With some parasites, you may find that the immune response that provides protection focuses on the sugars. If you can separate the sugary elements from the protein, that could make vaccine production even easier. That would mean that it just look at the structure of the parasite. sugar composition. If we manage to vaccinate with sugar structures, we can develop vaccines even faster. After all, in this case you no longer need to identify individual antigens .