Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides

Abstract

BackgroundSynthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen.MethodsIndividual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and designed to avoid IgE binding. Three sets of COPs were tested in vitro in competition ELISA and basophil degranulation assays. Their in vivo reactivity was determined by intraperitoneal challenge in rBet v 1 sensitized mice as well as by skin prick tests in volunteers with allergic rhinoconjunctivitis to birch pollen.ResultsThe combination, named AllerT, of three COPs selected for undetectable IgE binding in competition assays and for the absence of basophil activation in vitro was unable to induce anaphylaxis in sensitized mice in contrast to rBet v 1. In addition no positive reactivity to AllerT was observed in skin prick tests in human volunteers allergic to birch pollen. In contrast, a second set of COPs, AllerT4-T5 displayed some residual IgE binding in competition ELISA and a weak subliminal reactivity to skin prick testing.ConclusionsThe hypoallergenicity of contiguous overlapping peptides was confirmed by low, if any, IgE binding activity in vitro, by the absence of basophil activation and the absence of in vivo induction of allergic reactions in mouse and human. Trial registrationClinicalTrials.gov NCT01719133

On Peptides and Altered Peptide Ligands: From Origin, Mode of Action and Design to Clinical Application (Immunotherapy)

“…These piTregs are characterized by the phenotype CD25-CTLA-4+Foxp3- [172] and they reportedly express the transcription factors Tbet and Egr2 [173]. In principle, peptide immunotherapy represents an attractive therapeutic strategy, since it entirely focuses on T cell epitopes derived from major allergens (antigens), which are usually not recognized by the patients' IgE [174] and therefore their application should not bear the risk of anaphylactic reactions triggered by type I immune reactions. Peptides derived from Fel d 1, the major cat dander allergen, have already been tested in clinical studies and, in fact, positively influenced the course of the disease [175,176,177].…”

A randomized, double‐blind, placebo‐controlled, dose‐finding trial with Lolium perenne peptide immunotherapy

“…To achieve these goals, novel therapeutics have been developed to overcome the limitations of natural allergens’ intrinsic features. Recent investigations on peptide immunotherapy focus on synthetic peptide immunoregulatory epitopes (SPIREs) containing T cell–reactive short peptides2 and longer continuous overlapping peptides (COPs)3 of up to 80 amino acids 4. Sets of long COPs that encompass all potential T‐cell epitopes without IgE conformations induce IgG 4 but also evoke late asthmatic responses at high concentrations 4, 5…”

Immunotherapy in allergy and cellular tests

“…130 The recommended use of BAT in vaccination may give possible suggestions 23 but criticisms about its routine use and meaning are yet far to be fully prevented. However, most of the reported studies show BATs as simple confirmatory assay of allergen-induced desensitization, 198,199 while cellular test should indicate fundamental parameters in innate immunity involved in allergy desensitization, even during the maintenance protocol. Furthermore, BAT is frequently used to assess in vitro allergen immunotherapeutics, often as a probe to detect AIT working.…”

“…Furthermore, BAT is frequently used to assess in vitro allergen immunotherapeutics, often as a probe to detect AIT working. 199,200 These circumstances might deject researchers to use BAT as a finest diagnostic tool to probe basophilic cell behavior during allergy desensitization with immunotherapy. Even the role of membrane markers, the expression of which is elicited by an antiIgE mediated response, merits further attention.…”