Developing vaccines against gastrointestinal nematodes of sheep - the model matters

Different parasite challenge models have been used over many years in the development of novel vaccines against gastrointestinal nematodes of livestock. Typically, following vaccination with either native or recombinant proteins, the host animal is then given a bolus challenge of infective nematode larvae (iL3) or a trickle challenge where smaller numbers of iL3 are given at regular intervals over a period of time. The bolus method may be a robust test of whether high levels of vaccine-induced immunity translate to protection against a large pathogen insult, whereas the trickle infection method may be more appropriate to test the impacts of an exposure-induced anamnestic response. In the work presented here, three different models of testing gastrointestinal nematode vaccine efficacy were compared. Lambs (4-5 months old) were vaccinated with the excretory/secretory products collected from ex-vivo Teladorsagia circumcincta fourth stage larvae (L4ESP) and then challenged with a bolus of 5,000 iL3 or with a trickle infection where 2,000 iL3 were administered 3 times per week for 4 weeks (truncated trickle) or continuously challenged for 9 weeks (trickle) until post-mortem. Monitoring of faecal egg counts following challenge demonstrated that there was no significant impact of vaccination on cumulative faecal egg count (cFEC) following bolus challenge but, during the period of regular ingestion of iL3 in both trickle challenge models, statistically-significant reductions in the cFEC [(40-46 % reduction in mean cFEC (P < 0.05); 68-71 % reduction in median cFEC)] were observed. Shortly after cessation of the iL3 challenge in the truncated trickle challenge group, this protective effect of the vaccine on cFEC was lost whereas vaccine efficacy was maintained in the model with continued regular ingestion of iL3 (trickle challenge model, which most accurately reflect the parasite challenge in a field situation). In conclusion, the choice of challenge model had a profound impact on the ability to measure vaccine efficacy.