Allergen extracts for immunotherapy: to mix or not to mix?

ABSTRACT

Allergen immunotherapy (AIT) is established as a curative treatment for allergic rhinitis, asthma, as well as insect venom allergy. AIT is based on the administration of natural allergen extracts via the subcutaneous or sublingual routes to reorient the immune system towards tolerogenic mechanisms. In this regard, since many patients are poly-allergic, mixtures of allergen extracts are often used with a potential risk to cause allergen degradation, thereby affecting treatment efficacy. Herein, we discuss the advantages and drawbacks of mixing homologous (i.e., related) or heterogeneous (i.e., unrelated) allergen extracts. We provide evidence for incompatibilities between mixes of grass pollen and house dust mite extracts containing bodies and feces, and summarize critical points to consider when mixing allergen extracts for AIT.

KEYWORDS:

• Allergen
• allergen immunotherapy
• allergen extracts
• allergen mixtures
• homologous groups
• poly-sensitization

Financial & competing interests disclosure

This work was funded by Stallergenes. E Nony, A Martelet, K Jain and P Moingeon are employed by Stallergenes. 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.

Key issues

• A majority of allergic patients are polysensitized, with only a fraction being poly-allergic, which may be optionally treated either with single-allergen extracts administered sequentially or with a mixture of allergens.

• Allergen extracts used for immunotherapy are complex products containing multiple allergens and proteins, including often molecules with protease activity. Furthermore, the quality and composition of these allergen extracts vary dramatically between manufacturers.

• Differing therapeutic practices are implemented in the US and in Europe regarding the use of allergen extract mixtures, based on specific guidelines.

• In-depth characterization of mixtures of allergen extracts confirms that significant allergen proteolysis may occur within specific mixtures, for instance, associating pollen and mite extracts containing fecal particles. Such incompatibility between extracts can impair dramatically both therapeutic efficacy and safety.

• A combination of stability-indicative analytical methods (e.g. electrophoresis, immunological methods, chromatography, mass spectrometry) can be used to assess the compatibility between allergen extracts.

• Formulation and storage conditions should be defined to ensure the optimal stability of allergen mixtures.