Allergy caused by immunoglobulin (Ig) E is a common hypersensitivity condition worldwide. Two approaches are generally followed for the treatment of allergy - the first being drugs used to reduce allergic symptoms and the second approach involves the use of allergen-specific immunotherapies (AIT).
Antibodies, 3D rendering - Illustration Credit: ustas7777777 / Shutterstock
Pharmacotherapy to reduce allergic symptoms and inflammation is frequently used; however, these drugs can cause adverse effects, there is low clinical efficacy, and the effects diminish after discontinuation of therapy. High cost and the lack of disease-modifying effect are other disadvantages of traditional pharmacotherapy.
Interventions based on AIT involve the identification of the disease-causing allergens, allergen avoidance strategies, and the prescription of targeted immunotherapy. The treatment is based on the administration of the disease-causing allergens with the goal to induce a protective immune response. Even though the approach involves a longer treatment timeframe, the treatment effects are long-lasting. AIT also confers disease-modifying effects which halt the progression from mild-to-severe manifestations. The treatment is relatively inexpensive and may be also used for the prevention of allergic sensitization.
The quality of allergen extracts from natural sources is a major bottleneck for AIT. The instability and varying amounts of allergens, contamination, and poor immunogenicity of the allergens are major hurdles. Natural allergen extracts do not fulfil the requirements of regulatory authorities for allergy vaccine manufacturing. Additionally, the administration of such allergens can induce severe and life-threatening side effects and hence necessitate cumbersome up-dosing schemes with multiple injections and hospitalization.
The application of recombinant technologies for the production of recombinant allergens for AIT has opened up new avenues for the treatment of allergic diseases. With advancement in research, allergen-encoding complementary DNA (cDNA) for most clinically relevant allergens have been isolated. This has led to the production of recombinant forms of allergens in large quantities and at consistent quality. The first recombinant allergen for dust mite allergen Der p 1 was discovered in 1988.
Recombinant allergens in structure elucidation
Allergens naturally occur as a mixture of several isoforms, and separation of isoforms is a difficult task. Additionally, some allergens are present at very low concentrations; hence it is cumbersome to obtain a sufficient quantity of the purified allergen for crystallization. Recombinant allergens have helped to elucidate the crystal and solution structures of allergens.
Recombinant allergens in diagnostic tests
Because natural allergens can be isolated in only small quantities from natural sources, recombinant allergens have become an alternative for allergy diagnosis. Molecular diagnostic tests help to elucidate the sensitization patterns of a patient at the molecular level. This procedure increases diagnostic accuracy, distinguishes genuine sensitization from sensitization due to cross-reactivity, helps to assess the risk and type of allergic reaction, and facilitates the selection of eligible patients and suitable allergens for allergen-specific immunotherapy.
Recombinant allergens in vaccine production
The use of recombinant technologies in vaccine production has led to the production of well-characterized, noncontaminated vaccines with well-defined biologic activity. Genetic engineering techniques allow development of allergen derivatives with reduced IgE reactivity, a reduced risk of triggering undesirable allergic reactions, while retaining immunogenic activity.
Much progress has been made in the field of recombinant allergen development and application. These advances can be applied to improve research in basic scientific investigations, diagnosis, and therapy of human allergic diseases.