Th109 - Sialic Acids on House Dust Mite (HDM) Allergen, Der P 2, Shift Immune Responses Towards a Regulatory Profile

Esther C de Jong; Charlotte Castenmiller; Sandra J van Vliet; Hakan Kalay; Eleonora Nardini; Eveline RJ Li; Gaby van Barneveld; Yvette van kooyk; Ronald van Ree; Joyce Lubbers

Abstract Text: House Dust Mite (HDM) allergy affects more than 50 million people worldwide and is one of the most important risk factors for the development of asthma. Available allergen immunotherapy which consist of administering incremental doses of HDM allergen over a period of 3-5 years to induce tolerance, is lengthy and carries a high risk of severe side effects. Safer therapeutic options that can rapidly induce tolerance are therefore warranted. One of such therapeutic options includes the use of carbohydrate-based protein conjugates to target immunomodulatory receptors on the immune cells that are involved in the development of allergy. Sialic acid–binding immunoglobulin-like lectin-9 (Siglec-9) is an immunomodulatory receptor found predominantly on immune cells. It is an important negative regulator of acute inflammatory responses and is a potential target for the treatment of HDM allergy. We describe a Siglec-targeting platform consisting of an allergen of HDM, Dermatophagoides pteronyssinus (Der p 2), decorated with a natural Siglec-9 ligand, (α2→3) N-acetylneuraminic or sialic acid. Treatment of human peripheral blood mononuclear cells (PBMCs) with this glycoconjugate suppressed the production of allergy-associated inflammatory cytokine, interleukin-5 (IL-5) and augmented the expression of anti-inflammatory cytokine, IL-10. The glycoconjugate also suppressed the activation of CD4 T helper (Th) cells and induced the expansion of Tr1 regulatory T cells, known to suppress the function of pathologic Th cells. Collectively, these results demonstrate a promising potential of targeting Siglec receptors with glycan-based constructs for the rapid induction of an anti-inflammatory state in immune cells for short-lasting allergen immunotherapy against HDM allergy.