Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

Abstract

Conventional allergen-specific immunotherapy (AIT), based on administrations of allergen extracts, represents up to now the unique protocol for the desensitization of allergic patients. Whereas the effectiveness of AIT was evidenced for the treatment of allergic rhinitis and allergic asthma, such strategy remains experimental for food allergies up to now. However, important issues are commonly associated with AIT as the quality of natural allergen extracts, the long duration and adverse side-effects which negatively affect successful desensitization together with the patient compliance. The rapid progression of molecular allergology made possible the quest of safer, shorter and more effective immunotherapeutic approaches. The aim of this review was to provide an update on these different innovative recombinant derivatives including their efficacy but also their limitations. Despite promising preclinical and early clinical studies, the absence of convincing data in large phase III trials precludes so far the translation of these immunotherapeutic candidates into the clinic. K E Y W O R D S allergen-specific immunotherapy, blocking antibodies, clinical trial, efficacy, hypoallergenic, recombinant derivatives, safety, Treg Present AIT Delivery route SCIT SLIT Molecules Allergen extracts +/-Adjuvant Alum 26Abbreviations: 8x6Q2W, grass allergen peptides at 6 nmol at 2-wk intervals for a total of 8

Allergic rhinitis

“…Increasing safety while maintaining or even increasing efficacy are the main goals of research for novel vaccine development and improvement of treatment schemes in AIT. Perspectives in AIT are well established 181 , and many new products are in development [182][183][184][185] . However, the vast majority of previous attempts failed because safety issues or lack of efficacy was observed.…”

The evolution of allergen‐specific immunotherapy: The near and far future

“…Among these, CpG oligonucleotides (CpG-ODN) have already been tested in preclinical studies with positive clinical outcomes. 4 CpG-ODN suppresses Th2 response by binding to TLR-9, increasing IL-12, IL-10, and IL-22 and decreasing TLSP. CpG-ODN were also coupled to virus-like particles (VLP), which are composed of proteins that form the viral capsid and are used as platforms for immune recognition, uptake, and processing.…”

“…The direct conjugation of adjuvant molecules to allergens has also been proposed as another technique for improving AIT strategies. Among these, CpG oligonucleotides (CpG‐ODN) have already been tested in preclinical studies with positive clinical outcomes 4 . CpG‐ODN suppresses Th2 response by binding to TLR‐9, increasing IL‐12, IL‐10, and IL‐22 and decreasing TLSP.…”

“…Although natural allergen extracts remain the landmarks for AIT, attempts to use alternative immunotherapeutic candidates (eg, recombinant allergens, hypoallergenic derivatives, and peptides) are continuously emerging. The purpose of these innovative strategies is to improve the safety and efficacy of AIT while reducing the duration of treatment 4 . Recombinant wild‐type allergens contain IgE and T‐cell epitopes of natural allergens and could induce blocking allergen‐specific IgG antibodies by immunization and, eventually, T‐cell tolerance.…”

Immunotherapy, pre‐school wheeze and asthma

“…Although immunotherapy has been in use for over 100 years, innovations continue to be investigated to optimize this therapy 1 . Examples are peptide immunotherapy, recombinant allergens, epicutaneous immunotherapy and oral immunotherapy.…”