D3.226 - Prophylactic sublingual peanut immunotherapy alters antibody responses and downstream allergen reactivity in a Brown Norway rat model

Peanut allergy is an IgE-mediated food allergy characterised by a Th2-skewed immune response and mast cell activation following allergen exposure. Sublingual immunotherapy (SLIT) with peanut protein extract (PPE) is a promising strategy to promote immune tolerance, but the immunological mechanisms underlying treatment effects remain incompletely understood.

Brown Norway rats (n=16/group) received daily sublingual administration of either PPE or PBS (control) for three weeks. Subsets of rats (n=8/group) were euthanized either immediately after sublingual administration (20 µl per animal per day) or after subsequent intraperitoneal post-immunisations (50 µg PPE per animal, four injections) to evaluate immune responses during SLIT treatment and following allergen re-exposure. PPE-specific IgE, IgG1, and IgA levels in serum were measured by ELISA, and basophil activation was assessed using the basophil activation test (BAT). Longitudinal blood sampling enabled analysis of antibody dynamics over time. Clinical reactivity was assessed using ear-swelling measurements (10 µg PPE each ear) and symptom scoring after allergen challenge (100 mg/ml protein). 

SLIT-treated rats exhibited reduced sensitisation with significantly lower levels of IgE and reduced clinical reactivity with significantly lower levels of symptoms and degranulation response in BAT after allergen re-exposure when compared with control rats. The treatment was shown to modulate both PPE-specific IgG1 and IgA responses. It was shown that some rats became sensitised during SLIT, yet this sensitisation seemed not to be of clinical relevance as none of the rats had any symptoms upon oral allergen challenge. Together, these findings suggest an altered immune response following SLIT, leading to decreased response to allergen upon re-exposure, which forms the basis for analysing immune responses in more detail by use of omics techniques.

Peanut SLIT reduces allergic reactivity and induces broad immunological changes in this model. Beyond effects on IgE, IgG1, and basophil activation, SLIT significantly influences PPE-specific IgA responses, suggesting a role for mucosal immune modulation in the mechanism of action.