Abstract
Background The use of hypoallergenic derivatives is considered beneficial to promote the safety and efficacy of allergen-specific immunotherapy. We aimed to assess the efficacy of reduced and alkylated (R/A) Pru p 3, a hypoallergenic folding variant of the major peach allergen, in subcutaneous immunotherapy (SCIT) using a murine model of peach allergy. Methods and Results After sensitization with Pru p 3, BALB/c mice received SCIT with Pru p 3 or R/A Pru p 3 and were challenged with Pru p 3. SCIT with Pru p 3, but not with R/A Pru p 3, suppressed anaphylaxis upon the challenge significantly. SCIT with Pru p 3 did not suppress Pru p 3-specific IgE and IgG1 production, but enhanced IgG2a production. In contrast, SCIT with R/A Pru p 3 suppressed IgE and IgG1 production, but enhanced IgG2a production only moderately. The therapeutic efficacy of SCIT with Pru p 3 was associated with induction of IL-10 and IFN-γ. Conclusion Hypoallergenic folding variant of Pru p 3 is not likely an efficacious therapeutic component in SCIT of peach allergy. The lower efficacy of R/A Pru p 3 might be attributed to poor antigenicity and/or weak stability due to its unfolded conformation.
Highlights
The prevalence of food allergy has increased over the past decade
It has been thought that hypoallergens can be applied in higher doses due to reduced allergenicity and provide a safer and more effective treatment than the respective wild-type allergens
In the present study, we found that Pru p 3, the wild-type peach allergen, possesses a better therapeutic efficacy than reduced and alkylated (R/A) Pru p 3, a hypoallergenic folding variant, in subcutaneous immunotherapy (SCIT) to suppress development of anaphylaxis
Summary
The prevalence of food allergy has increased over the past decade. Allergen-specific immunotherapy (AIT) is the specific and disease-modifying approach to treat allergic diseases [1, 2]. To reduce the risk of adverse reactions, hypoallergenic variants with reduced IgE reactivity but with retained T-cell epitopes have been considered as safer and potentially more efficacious alternatives to the corresponding wild-type allergens [1, 4,5,6]. We aimed to assess the efficacy of reduced and alkylated (R/A) Pru p 3, a hypoallergenic folding variant of the major peach allergen, in subcutaneous immunotherapy (SCIT) using a murine model of peach allergy. SCIT with Pru p 3 did not suppress Pru p 3-specific IgE and IgG1 production, but enhanced IgG2a production. SCIT with R/A Pru p 3 suppressed IgE and IgG1 production, but enhanced IgG2a production only moderately. Hypoallergenic folding variant of Pru p 3 is not likely an efficacious therapeutic component in SCIT of peach allergy. The lower efficacy of R/A Pru p 3 might be attributed to poor antigenicity and/or weak stability due to its unfolded conformation
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