Project: Plants4Nemavax

Parasitic nematodes (roundworms) are amongst the most common pathogens in grazing ruminants worldwide. The continuous exposure to these worms has a significant impact on the health status and productivity of the animals.

Control of these infections currently relies almost completely on periodic mass administration of anthelmintic drugs. However, with the increasing incidence of anthelmintic resistance around the world, there is an urgent need for alternative control measures. Vaccination is often put forward as the most rational and cost-effective alternative to control infections with parasitic worms. In recent years it has been shown that it is possible to protect cattle and sheep against worm infections by vaccinating them with antigens isolated directly from the worms. Unfortunately, for most parasite species, this approach is unsustainable for large-scale application as it relies on infected host animals to produce the vaccines. The production of recombinant vaccines in heterologous expression systems seems the obvious solution. However, of all the recombinantly expressed subunit vaccines that were evaluated in the past, none induced sufficient levels of protection to consider further commercial development. One of the bottlenecks explaining why many vaccination trials with nematode vaccines have been unsuccessful is the inability of the expression systems to reconstitute worm antigens with their native post-translational glycan modifications. In this international collaborative project, we will reconstruct the sugar structures of native nematode proteins in our plant-based expression system by adapting the post-translational machinery of Nicotiana benthamiana plants. The aim of this project is to use this versatile plant-based production platform to express a set of well-defined nematode vaccine antigens and deliver proof-of-concept on the role of the glycans on vaccine efficacy against nematodes in cattle and sheep.