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

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

Authors: 
Rudolf Valenta, MDa,b,c, Alexander Karaulov, MDc, Verena Niederberger, MDd, Yury Zhernov, PhDb, Olga Elisyutina, MDb, Raffaela Campana, PhDa, Margarete Focke-Tejkl, PhDa, Mirela Curin, PhDa, Leyla Namazova-Baranova, MDe, Jiu-Yao Wang, MD, PhDf, Ruby Pawankar, MD, PhDg, and Musa Khaitov, MDb V.

aDepartment of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
bNRC Institute of Immunology FMBA of Russia, Moscow, Russia
cLaboratory for Immunopathology, Department of Clinical Immunology and Alergy, Sechenov First Moscow State Medical University, Moscow, Russia dDepartment of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
eDepartment of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia
fCenter for Allergy and Immunology Research (ACIR), College of Medicine, National Cheng Kung University (Hospital), Tainan, Taiwan
gDivision of Allergy, Department of Pediatrics, Nippon Medical School, Tokyo, Japan

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.

DOI: https://doi.org/10.1016/j.jaip.2018.08.032