Allergen Extracts for In Vivo Diagnosis and Treatment of Allergy: Is There a Future?

Abstract

Today, in vivo allergy diagnosis and allergen-specific immunotherapy (AIT) are still based on allergen extracts obtained from natural allergen sources. Several studies analyzing the composition of natural allergen extracts have shown severe problems regarding their quality such as the presence of undefined nonallergenic materials, contaminants as well as high variabilities regarding contents and biological activity of individual allergens. Despite the increasing availability of sophisticated analytical technologies, these problems cannot be overcome because they are inherent to allergen sources and methods of extract production. For in vitro allergy diagnosis problems related to natural allergen extracts have been largely overcome by the implementation of recombinant allergen molecules that are defined regarding purity and biological activity. However, no such advances have been made for allergen preparations to be used in vivo for diagnosis and therapy. No clinical studies have been performed for allergen extracts available for in vivo allergy diagnosis that document safety, sensitivity, and specificity of the products. Only for very few therapeutic allergen extracts state-of-the-art clinical studies have been performed that provide evidence for safety and efficacy. In this article, we discuss problems related to the inconsistent quality of products based on natural allergen extracts and share our observations that most of the products available for in vivo diagnosis and AIT do not meet the international standards for medicinal products. We argue that a replacement of natural allergen extracts by defined recombinantly produced allergen molecules and/or mixtures thereof may be the only way to guarantee the supply of clinicians with state-of-the-art medicinal products for in vivo diagnosis and treatment of allergic patients in the future.

A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens

“…Initial clinical trials were promising 47 but the large phase III field study ( https :// www.circa ssia.com/media/ press-relea ses/circa ssia-annou nces-topline-resul ts-from-cat-aller gy-phase-iii-study/ ) did not reveal significant differences regarding clinical improvement between active and placebo-treated patients. 48 Therefore, we suggest to use the hypoallergenic peptide mix rather in a preventive setting by applying the peptides systemically either via the oral route 16 or by injection, 49 with the goal to prevent allergic sensitization early in childhood.…”

Detection of genuine grass pollen sensitization in children by skin testing with a recombinant grass pollen hybrid

“…However, the accurate prescription of SIT depends on the correct identification of the culprit allergens, which can be facilitated by molecular allergy diagnosis . Skin testing represents a commonly used first diagnostic method in clinical practice, but its informative value is limited by the use of allergen extracts with varying and sometimes undefined composition . In addition, the presence of cross‐reactive allergens in various extracts often impedes the determination of the sensitizing allergen source, especially in polysensitized patients .…”

“…[9][10][11] Skin testing represents a commonly used first diagnostic method in clinical practice, but its informative value is limited by the use of allergen extracts with varying and sometimes undefined composition. 12,13 In addition, the presence of cross-reactive allergens in various extracts often impedes the determination of the sensitizing allergen source, especially in polysensitized patients. 9 In southern Europe, the overlapping pollination seasons and an abundance of multisensitization profiles make it even more difficult to distinguish among sensitizations to different pollen allergens.…”

Molecular allergy diagnosis: A potential tool for the assessment of severity of grass pollen‐induced rhinitis in children

“…In this setting, the in vivo challenge tests, in particular skin testing, are used to link IgE sensitization to certain allergens to the development of allergic symptoms. 1 At present, only allergen extract-based tests are available for in vivo diagnosis. But since allergen extracts have been classified as medical products by the European Directive 2001/83/EC, increased regulatory demands have prompted manufacturers to reduce the number of available extracts for economic reasons over the past few years and it can be expected that allergen extract-based provocation tests may disappear from the market in the future.…”

“…But since allergen extracts have been classified as medical products by the European Directive 2001/83/EC, increased regulatory demands have prompted manufacturers to reduce the number of available extracts for economic reasons over the past few years and it can be expected that allergen extract-based provocation tests may disappear from the market in the future. 1 Moreover, diagnostic allergen extracts were shown to provide only limited clinical information due to quality matters and the presence of cross-reactive allergens as well as clinically non-relevant IgE-reactive carbohydrates. 1 As these problems are an inherent part of the production process and its starting material, they cannot be resolved by improving allergen extract-based technology.…”