Introduction:
Epicutaneous immunotherapy (EPIT) with the VIASKIN® patch technology has emerged as a promising new class of immunotherapy for treatment of food allergies. EPIT aims at leveraging the potential of the skin’s immune system to promote immune modulation while limiting systemic exposure, by regularly applying antigens to the non-vascularized epidermis. We hypothesized that EPIT could be harnessed to modulate the pathological immune response to gluten in celiac disease (CeD) and designed a multi-epitope peptide (Av6), encompassing key α-, γ- and w-gliadin epitopes, and expected to be suitable for use as a drug substance in EPIT. Here, we sought to evaluate whether Av6 could modulate antigen-specific immune responses in HLA-DQ8 mice when applied onto intact skin using epicutaneous patches.
Materials & Methods:
HLA-DQ8 mice were treated for 6 weeks with a total of 11 epicutaneous patches containing 10 or 100 µg Av6. After 2 weeks of treatment, mice were immunized subcutaneously with 100 µg Av6 and boosted 2 weeks later with 50 µg Av6. Blood and spleen were collected after 6 weeks. Anti-gliadin and anti-Av6 IgG1 or IgG2c serum levels were measured by ELISA. Splenocytes were restimulated in culture for 3 days with Av6 or 4 smaller peptides corresponding to Av6’s individual moieties, and cytokines were quantified in supernatants by multiplex ELISA.
Results:
Epicutaneous treatment with Av6 modulated the gliadin-specific humoral response, reducing IgG2c (Th1-associated) and increasing IgG1 (Th2-associated) antibody responses. Consistently, epicutaneous treatment with Av6 also modulated the specific T-cell response, evidenced by increased secretion of Th2 cytokines IL-4 and IL-5 and concomitant decreased secretion of IFN-g by splenocytes restimulated with Av6 or peptide moieties comprising DQ8-restricted epitopes.
Summary:
This study demonstrates that Av6 engages with the immune system of HLA-DQ8 mice when administered epicutaneously, supporting the development of Av6 as a drug substance for EPIT in CeD.