Recombinant Allergens in Specific Immunotherapy

Genetically engineered recombinant allergens have the ability to improve allergy diagnosis and are used as reference standards for analytical methods. In addition, the use of recombinant allergens in allergen-specific immunotherapy has long been considere

  • PDF / 504,739 Bytes
  • 14 Pages / 439.37 x 666.142 pts Page_size
  • 49 Downloads / 167 Views

DOWNLOAD

REPORT


26

A. Nandy, P.S. Creticos, and D. Häfner

26.1 Introduction Extract-based allergen-specific immunotherapy (AIT) has long been established as an effective treatment method for a wide variety of type-1 allergies including seasonal allergic rhinitis/conjunctivitis, perennial allergic rhinitis/conjunctivitis, allergic asthma, and venom sensitivity. Unmodified or chemically modified extracts with reduced immunoglobulin-E (IgE) reactivity, i.e., allergoids that can be used at higher doses, are finding application. Since extracts are natural products, their allergen contents can differ from one another according to raw material and extraction method. As a result, extract standardization is realistically limited to only total IgE-binding activity and quantification of the most relevant major allergen. Moreover, extracts are largely made up of components that can be considered unnecessary or even counterproductive for effective AIT. These include minor allergens in low concentrations, nonallergenic

The present chapter is based on, and modified from, an article by the authors published in 2015 in Allergo Journal International (Nandy A, Häfner D, Klysner S: Recombinant allergens for specific immunotherapy: Current concepts and developments. Allergo J Int 2015; 24:143–151). A. Nandy, PhD (*) Business Unit Allergy, Research & Development, Allergopharma GmbH and Co. KG, Reinbek, Germany e-mail: [email protected] P.S. Creticos, MD, Prof. Johns Hopkins University School of Medicine, Division of Allergy and Clinical Immunology, Baltimore, MD, USA Creticos Research Group, LLC, Crownsville, MD, USA D. Häfner, PhD Allergopharma GmbH and Co. KG, Reinbek, Germany © Springer International Publishing Switzerland 2017 J. Kleine-Tebbe, T. Jakob (eds.), Molecular Allergy Diagnostics, DOI 10.1007/978-3-319-42499-6_26

473

474

A. Nandy et al.

1

NA

RA 2 3

1

1

3

1

IA 2

MA

Recombinant allergens

Natural extracts

Only relevant allergens Therapeutic relevance

Number of molecules

Major allergens (MA) Intermediate allergens (IA) Minor allergens (MiA) Non-allergens (NA)

Fig. 26.1  Natural extracts are made up of a mixture of relevant allergens, intermediary allergens, minor allergens, and a large quantity of undefined nonallergenic materials (e.g., proteins, sugars, lipids). Genetically engineered allergens, in contrast, comprise only those components relevant to treatment, can be precisely standardized, and can be reproduced to consistent quality. According to the concept of major allergens, preparations for recombinant treatment are made up of a cocktail of relevant allergens (e.g., grasses, house dust mites) or can be obtained as a monopreparation in cases where only one relevant major allergen is available (e.g., birch, cat, ragweed)

proteins, lipids, sugar, or other components that have not been further characterized (⦿ Fig. 26.1). In contrast, genetically engineered allergens can be characterized extensively and can be produced in a reproducible manner to a quality that meets the regulatory requirements for pha