Abstract
Covalent conjugation of allergens to toll-like receptor (TLR) agonists appears to be a powerful strategy for the development of safety compounds for allergen-specific immunomodulatory response toward tolerance in allergy. In this work, we have synthesized two family of ligands, an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-b]indole as a ligand for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible for LTP-dependent food allergy. These conjugates interact with dendritic cells, inducing their specific maturation, T-cell proliferation, and cytokine production in peach allergic patients. Moreover, they increased the Treg-cell frequencies in these patients and could induce the IL-10 production. These outcomes were remarkable in the case of the TLR7 ligand conjugated with Pru p 3, opening the door for the potential application of these allergen–adjuvant systems in food allergy immunotherapy.
Highlights
Food allergy (FA) is currently a burden for the Health Systems mainly in western European countries where the prevalence is increasing with plant origin as the main triggers in both adult and adolescent populations.[1]
We have addressed the immunological response induced by compounds that include, besides the TLR4 or TLR7 agonists, a synthetic peptide of the allergenic epitope Pru p 3 (Pp3), TLR4lig-Pp3, and TLR7lig-Pp3, respectively, in cells from lipid transfer protein (LTP) allergic patients and analyzed the type of response in order to assess the modulatory capacity of these ligands
We have focused our efforts to prepare a TLR4 agonist based on pyrimido[5,4-b]indole derivatives
Summary
Food allergy (FA) is currently a burden for the Health Systems mainly in western European countries where the prevalence is increasing with plant origin as the main triggers in both adult and adolescent populations.[1]. Novel vaccines that overcome such inconveniences are in demand
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