Poster Presentation International Celiac Disease Symposium 2026

Design and In Vitro Validation of a Multi-Epitope Peptide Construct as a Novel Drug Substance Candidate Adapted to Epicutaneous Immunotherapy (EPIT) in Celiac Disease (#252)

Amy K Russell 1 , Melinda Y Hardy 1 , Vincent Dioszeghy 2 , Katie Matthews 2 , Pierre-Louis Hervé 2 , Stef Koppelman 3 , Hugh A Sampson 4 , Jason A Tye-Din 1 5
  1. Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC, Australia
  2. DBV Technologies, Châtillon, France
  3. Food Allergy Research and Resource Program, Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
  4. The Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
  5. Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Victoria, Australia

Introduction:

Epicutaneous immunotherapy (EPIT) with the VIASKIN® patch technology represents a potential new immunotherapy approach, with demonstrated ability to desensitize food-allergic children. By delivering antigens through intact skin, EPIT aims at leveraging the skin’s propensity to promote immune modulation, while limiting systemic antigen exposure. We hypothesized that EPIT could potentially address celiac disease (CeD) by modulating the pathological immune response to gluten. However, developing a suitable drug substance from gluten presents significant challenges. To address this, we designed a multi-epitope peptide construct (Av6) encompassing key HLA-DQ2- and/or HLA-DQ8-restricted α-, γ- and w-gliadin epitopes, meeting EPIT requirements. As a first step, we assessed whether Av6 could be efficiently processed and presented as gliadin epitopes by evaluating its ability to reactivate gliadin-specific human T cells.

Methods:

Av6 was evaluated using complementary whole blood interleukin (IL)-2 release and IFN-γ ELISpot assays. Whole blood from treated CeD participants (HLA-DQ2.5+, n=6; non-HLA-DQ2.5+, n=4) and HLA-matched healthy controls (n=3) was stimulated with Av6 (0.5–10 µM), and IL-2 quantified (MSD S-Plex). Epitope-specific reactivation was assessed by IFN-γ ELISpot using DQ2.5-glia-α1a-, α2-, ω1-, and ω2-specific T-cell clones and a DQ8-glia-α1-specific T-cell line.

Results:

Av6 induced robust IL-2 release in both HLA-DQ2.5+ and non-HLA-DQ2.5+ CeD cohorts. At 2.5 µM Av6, mean IL-2 concentrations were 4,372 fg/mL in HLA-DQ2.5+ CeD and 5,221 fg/mL in non-HLA-DQ2.5+ CeD, compared with 114 fg/mL in healthy controls. In IFN-γ ELISpot, 2.5 µM Av6 reactivated 5/5 gliadin-specific T-cell clones/lines, with responses comparable to or approaching those elicited by cognate peptides: DQ2.5-glia-α1a (100%), -α2 (130%), -ω1 (52%), -ω2 (89%) and DQ8-glia-α1 (103%), confirming the functional integrity of these epitopes within Av6.

Conclusion:

Av6 contains functional HLA-DQ2.5- and HLA-DQ8-restricted epitopes that are processed, presented, and recognised by CeD-relevant pathogenic gluten-specific CD4+ T cells in vitro, supporting Av6 as a drug substance candidate for EPIT in CeD.