Low-Dose Allergen-Specific Immunotherapy Induces Tolerance in a Murine Model of Shrimp Allergy

Abstract

Background: The efficacy and safety of allergen-specific immunotherapy (AIT) are highly dose-dependent. Methods: We investigated the dosage effects of AIT and the underlying mechanisms in a murine model of shrimp hypersensitivity. BALB/c mice were sensitized with recombinant shrimp allergen rMet e 1 and challenged orally with a high dose of rMet e 1 to elicit an allergic response. These sensitized mice were then treated with a low (0.01 mg), medium (0.05 mg), or high dosage (0.1 mg) of rMet e 1 intraperitoneally before receiving a second oral challenge. The allergic responses and immunological changes in the gut were compared between animals receiving different dosages. Results: We found that all sensitized mice that received rMet e 1 immunotherapy were desensitized, regardless of the dosage, and protected at the second oral challenge. Nevertheless, the mice in the high-dosage group experienced severe systemic reactions during the treatment phase. In contrast, regulatory T (T_reg) cell-associated genes were upregulated only in the low- and medium-dosage groups, and Foxp3+ cells were more abundant in the gut lymphoid tissues than in the high-dosage group. Conclusions: Our results demonstrate that low-dosage immunotherapy favors the induction of local Foxp3+ T_reg cells and the upregulation of regulatory cytokines. The safety advantages and long-term efficacy of low-dosage immunotherapy should be taken into consideration when developing immunotherapy dose schedules.

Glycosylated nanostructures in sublingual immunotherapy induce long-lasting tolerance in LTP allergy mouse model

“…One interesting finding is that D 1 ManPrup3 only induced a long-term beneficial effect when administered at 2 nM. This long term effect obtained with D 1 ManPrup3 at 2 nM was associated with the induction of FoxP3 + Treg cells and IL-10 production, both of which are thought to be essential in tolerance induction 33,34 . Higher concentrations of 5 nM, induced a protective effect initially, however this disappeared after 5 weeks.…”

Overcoming Shellfish Allergy: How Far Have We Come?

“…Specific immunotherapy using the causal allergen is the conventional treatment option for most food allergies, but adverse events during treatment are likely, as shown by our group [58]. Modifying recombinant allergens to reduce their IgE reactivity and allergenicity is a core strategy in improving the safety of AIT.…”

“…Our group recently investigated the dose-dependent effect and safety of recombinant tropomyosin Met e 1 in a murine model of shrimp hypersensitivity [58]. BALB/c mice induced with shrimp allergy were treated thrice by low (0.01 mg), medium (0.05 mg) or high (0.1 mg) rMet e 1 through the intraperitoneal route.…”

Recent Advances in Experimental Allergy

“…Leung et al [65] investigated the use of allergen-specific immunotherapy in the context of shrimp allergy in a mouse model. Recombinant shrimp allergen rMet e 1 was used to sensitize BALB/c mice, which was subsequently challenged.…”

“…Furthermore, the upregulation of Treg-associated genes was only observed in the low and moderately dosed groups and these groups exhibited higher numbers of Foxp3 + cells in the gut when compared to the high-dosage group. This work underlines the potential of allergen-specific immunotherapy as treatment for shrimp allergy and that dosage may play an important role in safety and efficacy [65]. Tools to study shellfish allergy are also continually being developed and refined.…”