Current developments for improving efficacy of allergy vaccines

Abstract

Allergic diseases are prevalent worldwide. Allergen immunotherapy (AIT) is a current treatment for allergy, leading to modification of the natural course of disease. Mechanisms of efficacy include Treg through release of IL-10 and TGF-β and specific IgG₄ blocking antibodies. Subcutaneous and sublingual routes are popular, but uptake is limited by inconvenience and safety concerns. Inclusion criteria limit application to a small proportion of allergic patients. New forms of immunotherapy are being investigated for more efficacious, convenient and safer options with promising advances in recent years. The rationale of reducing vaccine allergenicity to increase safety while improving immunogenicity led to investigation of T-cell epitope-based peptides and recombinant allergen derivatives. Additionally, different routes of administration and adjuvants and adjunct therapies are being explored. This review discusses the current status of AIT and recent advances to improve clinical efficacy, safety and long-term immune tolerance.

Keywords:

• adjuvant
• allergen immunotherapy
• allergic rhinitis
• allergy vaccine
• asthma
• recombinant allergen
• Treg
• sublingual immunotherapy
• T-cell anergy
• T-cell epitope peptide

Financial & competing interest’s disclosure

R O’Hehir and J Rolland are inventors of peanut SPIRE therapy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Allergic diseases are a major health and economic burden worldwide and current therapies are limited in application and efficacy.

• Current allergen immunotherapy (AIT) results in clinical improvement in patients meeting selection criteria and modifies the natural course of allergic diseases.

• AIT with whole extracts is associated with IgE-related side effects including large local reactions and systemic adverse events including anaphylaxis, limiting its application in clinical practice.

• Adherence to subcutaneous and sublingual immunotherapy is poor and better strategies to improve regimens, absorption, safety and efficacy are needed.

• Long-term tolerance is an important goal of allergy vaccines which is variably achieved with current regimens and extracts.

• Optimization of new allergy vaccines, in particular synthetic peptide immuno-regulatory epitopes, and delivery routes, in particular transdermal, should improve efficacy, safety and long-term immune tolerance.