Recombinant Allergens for Immunotherapy: State of the Art

Yury Zhernov; Mirela Curin; Musa Khaitov; Alexander Karaulov; Rudolf Valenta

Disclosures

Curr Opin Allergy Clin Immunol. 2019;19(4):402-414. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: More than 30 years ago, the first molecular structures of allergens were elucidated and defined recombinant allergens became available. We review the state of the art regarding molecular AIT with the goal to understand why progress in this field has been slow, although there is huge potential for treatment and allergen-specific prevention.

Recent findings: On the basis of allergen structures, several AIT strategies have been developed and were advanced into clinical evaluation. In clinical AIT trials, promising results were obtained with recombinant and synthetic allergen derivatives inducing allergen-specific IgG antibodies, which interfered with allergen recognition by IgE whereas clinical efficacy could not yet be demonstrated for approaches targeting only allergen-specific T-cell responses. Available data suggest that molecular AIT strategies have many advantages over allergen extract-based AIT.

Summary: Clinical studies indicate that recombinant allergen-based AIT vaccines, which are superior to existing allergen extract-based AIT can be developed for respiratory, food and venom allergy. Allergen-specific preventive strategies based on recombinant allergen-based vaccine approaches and induction of T-cell tolerance are on the horizon and hold promise that allergy can be prevented. However, progress is limited by lack of resources needed for clinical studies, which are necessary for the development of these innovative strategies.

Introduction

Immunoglobulin E (IgE)-associated allergy is the most common immunologically mediated hypersensitivity disease world-wide.[1,2,3] The analysis of the development of IgE sensitization to allergens in birth cohorts has made major progress through the use of micro-arrayed allergen molecules, which allow studying the development of IgE sensitization in childhood towards a large number of allergen molecules.[4–8,9] There are two major approaches for the treatment of allergy. One possibility is based on the reduction of allergic inflammation by pharmacotherapy and/or biologics.[10,11] Major disadvantages of symptomatic treatments are that the effects of treatment are gone immediately after discontinuation of therapy, that there is no beneficial disease-modifying effect, the clinical efficacy is lower than that of allergen-specific immunotherapy (AIT) and the costs for biologics are extremely high.[12] The second approach for treatment is based on allergen-specific forms of intervention. This approach requires the identification of the disease-causing allergens as rational basis for allergen avoidance strategies as well as for prescription of the correct AIT.[13] The need for detailed diagnosis may be considered as a disadvantage of allergen-specific treatment but has been greatly facilitated by molecular allergy diagnosis.[4,14,15,16,17] Major advantages of AIT are that the treatment is relatively inexpensive, it is highly effective if performed with high-quality allergens, treatment effects are long-lasting after discontinuation if the treatment was performed for more than 2 years and AIT has disease-modifying effects preventing the progression from mild-to-severe manifestations.[12,18] Importantly, allergen-specific forms of intervention may be also used for the prevention of allergic sensitization.[19–22]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....