Attempts to induce tolerance to Trichostrongylus colubriformis infection in sheep

Background and objectives

The possibility of manipulating the immune response in lambs to the gastrointestinal nematode Trichostrongylus colubriformis to reduce production losses associated with infection was investigated. In a series of four experiments, attempts to immunize sheep via the mucosal route to modify the immune response and induce mucosal tolerance are outlined. Initially, a proof of concept study was conducted with lambs being injected with multiple doses of a somatic T colubriformis antigen without an adjuvant in the rectal submucosa and subsequently challenged with T colubriformis L3 larvae. This was followed by a dose-response study comparing different antigen doses to identify the optimum dose of the nematode antigen for successful induction of mucosal tolerance. The final two studies were conducted to determine the larval stage specificity of the parasite antigen and the most suitable site of delivery required to stimulate mucosal tolerance.

Methods

In the proof of concept study, lambs either received repeated injections in the rectal submucosa at 3 × weekly intervals with 15 µg of L3, 11 µg of L4 and 21 µg of immature adult (L5) somatic T colubriformis antigens (ANT) or not (INF) prior to infection with T colubriformis. In the dose-rate study, antigen dose rates of 100%, 50%, 10%, 1% or 0% of the antigen concentration used in the proof of concept study were compared while the larval stage study compared antigen from either L3, L4, L5 stages or combination of all (COMB) and the route of administration study compared antigen delivery into either the rectal submucosa (RE) or sub-cutaneous injection (SC).

Results

During infection, lamb growth was improved by antigen treatment between days 21 and 42 in the proof of concept study (P = .009), for groups 10%, 50% and 100% in the dose-rate study (P < .05 for all) and in RE in the route of administration study with no improvement observed in the larval stage study. No differences in faecal egg counts were observed (P > .05 for all). Parasite-specific IgA and IgE showed a dose-response (the dose-rate study), were not affected by larval stage (the larval stage study) and were greater in RE than SC (the route of administration study). IL-4 production following lymphocyte stimulation was greatest in COMB (the larval stage study) and RE (the route of administration study).

Conclusions

Although antigen treatment improved performance, this was inconsistent and appeared to stimulate immunity rather than induce tolerance. Combined larval stages were more efficient than individual stages, and intra-rectal administration was more effective than sub-cutaneous.