Protective capacity of a recombinant vaccine against the cattle parasite Ostertagia ostertagi relies on engineering its native N-glycan composition

  • Myrna Bunte (Speaker)

Activity: Talk or presentationOral presentationAcademic

Description

With the rising resistance against anthelmintic drugs, a more sustainable control strategy against parasitic nematode infections in livestock, such as vaccination, is required. Vaccination with native activation-associated protein 1 from the economically important cattle parasite Ostertagia ostertagi (Oo-ASP-1) have demonstrated to induce protection. However, collecting large quantities of Oo-ASP-1 is difficult as it requires inoculation and sacrifice of large numbers of animals, which is labour-intensive, time-consuming and ultimately unsustainable for large-scale production. For this reason, vaccine development is dependent on recombinant expression of this protein. Attempts have been made to express Oo-ASP-1 in, for instance, yeast and baculovirus expression systems, but failed to confer the same level of protective capacity as native Oo-ASP1 due to difference in protein folding and post-translational modifications. Here, we show that glyco-engineering native glycan structures on recombinant Oo-ASP-1 expressed in Nicotiana benthamiana restores the protective capacity of native Oo-ASP-1. Recombinant Oo-ASP-1 is easily expressed in high quantities in N. benthamiana and subsequently purified without complex downstream processing. Furthermore, the N-glycosylation of native Oo-ASP-1 is mimicked by co-expression of specific glycosyltransferases. In vaccination trials, calves vaccinated with recombinant Oo-ASP-1 demonstrated a reduction in faecal egg counts and a significant increase in local IgG1 and IgG2 antibody responses, which correlates with protective immunity. These results indicate that mimicking the native N-glycan composition of Oo-ASP-1 in N. benthamiana is required for vaccine efficacy. Furthermore, these results demonstrate that N-glycosylation is an essential component for developing effective recombinant vaccines against parasitic nematodes.
Period17 Jan 2023
Event titleGlycoBioTec conference
Event typeConference
LocationBerlin, GermanyShow on map
Degree of RecognitionInternational