A team of researchers from the Netherlands, Belgium, and the UK has developed a novel vaccine against a stomach worm that infects millions of cattle worldwide.
The vaccine is based on modifying the sugar structures in a plant to mimic the parasite's surface molecules and trigger an immune response in the animals.
The problem of Ostertagia ostertagi
Ostertagia ostertagi is a nematode parasite that lives in the abomasum, the fourth stomach of ruminants.
It causes a disease called ostertagiosis, which is characterized by weight loss, reduced milk production, diarrhea, and sometimes death.
The parasite has a complex life cycle that involves eggs, larvae, and adult worms.
The larvae can enter a dormant state in the stomach wall, making them resistant to most anthelmintic drugs. The disease is estimated to cost the global cattle industry more than $2 billion per year.
The solution of plant glycoengineering
The researchers used a technique called plant glycoengineering to create a vaccine candidate against Ostertagia ostertagi.
Plant glycoengineering is the manipulation of the sugar structures (glycans) that are attached to proteins and lipids in plants.
These glycans can affect the biological functions and interactions of the molecules they decorate. By modifying the plant glycans, the researchers were able to produce proteins that resemble the parasite's surface antigens, which are the molecules that the host's immune system recognizes and attacks.
The researchers chose the tobacco plant Nicotiana benthamiana as the host for their vaccine production. They introduced genes from the parasite and from other organisms into the plant to generate the desired glycan structures.
They also used a gene-silencing technique to suppress the plant's glycan synthesis. The result was a plant that expressed parasite-like proteins with highly fucosylated glycans, which are rare in plants but abundant in nematodes.
The researchers then purified the plant-produced proteins and tested them as a vaccine in mice.
They found that the vaccine induced a strong antibody response against the parasite antigens, and also conferred protection against a challenge infection with Ostertagia ostertagi larvae.
The vaccine reduced the worm burden in the mice by 74% compared to a control group.
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The implications and challenges of the study
The study demonstrates the potential of plant glycoengineering as a platform for developing vaccines against metazoan parasites, which are difficult to target with conventional methods.
The plant system offers several advantages, such as low cost, scalability, safety, and flexibility.
The researchers hope that their vaccine could be applied to other ruminant parasites, such as Haemonchus contortus, which causes a similar disease in sheep and goats.
However, the study also faces some challenges and limitations. The vaccine has only been tested in mice, and it is not clear if it will be effective and safe in cattle.
The researchers acknowledged that they need to optimize the vaccine formulation, dosage, and delivery method for large animals. They also need to evaluate the vaccine's stability, shelf life, and regulatory compliance.
Furthermore, the vaccine may not be able to prevent the emergence of drug-resistant parasites, which is a growing threat in the livestock sector.
The researchers plan to conduct further studies to address these issues and to move their vaccine closer to the market.
They also hope that their work will inspire more research on plant glycoengineering and its applications in biotechnology and medicine.
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