Peptide allergen‐specific immunotherapy for allergic airway diseases—State of the art

Abstract

Allergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission.Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4 + T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.

One hundred and ten years of Allergen Immunotherapy: A journey from empiric observation to evidence

“…122 In addition to their innate immune stimulatory function, adju- Combining adjuvants also has the potential to be an effective strategy in infectious diseases/cancer therapy, and thus may prove beneficial in AIT. 114,[117][118][119]124,125 A variety of approaches have been adopted to reduce the allergenicity of AIT preparations. Building on the established practice of chemical modification of proteins to generate allergoids, several novel strategies including genetic mutation to alter structure (e.g., to remove disulfide bridges), recombinant fusion of proteins to enhance allergen uptake and processing (e.g., fusion of HIV trans-activator of transcription; TAT peptide, and an invariant chain fragment to allergen), production of large recombinant fragments, synthetic peptides (ranging from 71 amino acids to as few as 13), hydrolyzed allergens (generating fragments of 1-10 kDa), major allergen trimers, selection of natural hypoallergenic mutants, and hybrid molecules containing B-cell epitopes fused to non-allergen carrier proteins.…”

“…Building on the established practice of chemical modification of proteins to generate allergoids, several novel strategies including genetic mutation to alter structure (e.g., to remove disulfide bridges), recombinant fusion of proteins to enhance allergen uptake and processing (e.g., fusion of HIV trans‐activator of transcription; TAT peptide, and an invariant chain fragment to allergen), production of large recombinant fragments, synthetic peptides (ranging from 71 amino acids to as few as 13), hydrolyzed allergens (generating fragments of 1–10 kDa), major allergen trimers, selection of natural hypoallergenic mutants, and hybrid molecules containing B‐cell epitopes fused to non‐allergen carrier proteins. Several of these approaches have shown promise in phase 2 clinical trials, but few have been evaluated in phase 3 field studies, and with mixed results 114,117,125 …”

Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy

“…Currently, AIT is the only treatment capable of changing the course of the disease in patients with IgE-associated allergy [ 25 ]. AIT is considered a therapeutic vaccine that establishes tolerance against specific allergens [ 26 ].…”

Biomarkers in asthma and allergic diseases

“…A recent study by Luce et al 8 investigated the changes related to the recently described T helper type 2 lineage in allergic diseases (Th2A) following AIT. Successful AIT 9 has been associated with the induction of regulatory T cells (Tregs) and elevated allergen‐specific blocking immunoglobulin G4 (IgG4) antibodies that compete with IgE, subsequently dampening allergic inflammation. However, less is known about shifts in the effector cell compartment associated with AIT response.…”