Plant-based production of protective vaccine antigen against the bovine abomasal parasite Ostertagia ostertagi

Gastro-intestinal nematode infections pose a persistent threat to livestock health, welfare, and farm productivity. The conventional approach to control these infections involves the periodic use of anthelmintic drugs, but the increasing prevalence of anthelmintic resistance renders this approach unsustainable in the long term. With limited new drug compounds in the pipeline, immunological control of nematode infections through vaccination has been explored over the years and is considered promising with regards to sustainability and cost-effectiveness. However, progress in this area has been disappointing, especially with recombinant produced antigens. The reason for failure is often attributed to the inability of the expression systems to reconstitute the native antigens in terms of protein folding and post-translational modifications, such as N-glycosylation. Research on an experimental vaccine against the bovine abomasal parasite Ostertagia ostertagi recently indicated that the N-linked glycans on the native antigen were important in antibody recognition, in particular the presence of a core α1,3-fucose residue. By adapting the post-translational machinery of Nicotiana benthamiana, it was possible to produce recombinant glycoforms of the O. ostertagi ASP carrying the same hybrid-type glycans as the native version, including core fucose. ELISA assays performed with serum from calves vaccinated with the native ASP showed a higher affinity for the N. benthamiana versions of the antigen compared to a non-protective recombinant version produced in Pichia pastoris. Subsequent vaccination and challenge studies in cattle with the newly expressed recombinants resulted in a significant reduction (39%) of faecal egg output. These findings are highly promising for the field of anti-nematode vaccine development, as the transition from native to recombinant subunit vaccines for various parasitic nematodes has been difficult.