Allergen Peptides, Recombinant Allergens and Hypoallergens for Allergen-Specific Immunotherapy

Abstract

Opinion statementAllergic diseases are among the most common health issues worldwide. Specific immunotherapy has remained the only disease-modifying treatment, but it is not effective in all patients and may cause side effects. Over the last 25 years, allergen molecules from most prevalent allergen sources have been isolated and produced as recombinant proteins. Not only are these molecules useful in improved allergy diagnosis, but they also have the potential to revolutionize the treatment of allergic disease by means of immunotherapy. Panels of unmodified recombinant allergens have already been shown to effectively replace natural allergen extracts in therapy. Through genetic engineering, several molecules have been designed with modified immunological properties. Hypoallergens have been produced that have reduced IgE binding capacity but retained T cell reactivity and T cell peptides which stimulate allergen-specific T cells, and these have already been investigated in clinical trials. New vaccines have been recently created with both reduced IgE and T cell reactivity but retained ability to induce protective allergen-specific IgG antibodies. The latter approach works by fusing per se non-IgE reactive peptides derived from IgE binding sites of the allergens to a virus protein, which acts as a carrier and provides the T-cell help necessary for immune stimulation and protective antibody production. In this review, we will highlight the different novel approaches for immunotherapy and will report on prior and ongoing clinical studies.

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

“…Additionally, crude extracts also contain numerous nonprotein constituents such as chitins, β‐glucans, and endotoxins, all of which can act on innate immune cells in a pro‐inflammatory fashion, which might interfere with the tolerance‐inducing capacity required for successful therapy 7. In contrast, use of purified proteins allows for treatment with specific allergens in the absence of such components contained within extracts 8. This is expected to enhance SIT efficacy by more efficiently inducing a tolerogenic response due to the absence of TLR agonists during allergen administration, harnessing an immunoregulatory phenotype of the allergen‐presenting cell upon SCIT 1.…”

“…This is expected to enhance SIT efficacy by more efficiently inducing a tolerogenic response due to the absence of TLR agonists during allergen administration, harnessing an immunoregulatory phenotype of the allergen‐presenting cell upon SCIT 1. Moreover, use of purified allergens in combination with a component‐resolved diagnosis of sensibilization patterns holds the promise of personalized intervention strategies in immunotherapy 8. However, it is currently unknown whether purified allergens are a more efficient treatment modality than full allergen extracts.…”

Possibility for Allergy Immunotherapy with Long Synthetic Peptide of Bet V1

“…This approach has a history of over 100 years and has been advancing with methods such as use of peptides, recombinant proteins and hypoallergens with the aim of improving safety in patients [1,2]. Traditional AIT is performed by subcutaneous injection (SCIT).…”

Control Process for Manufacturing and Standardization of Allergenic Molecules

“…Moreover, with the release and coming into force of specific guidelines for the allergen manufacturing process and the new regulatory requirements of international agencies published in the last 5-6 years, the concept of natural and allergenic vaccines is being modified and adapted to the modern pharmaceutical products standards. Additionally, new products are being developed under the umbrella of immunological-based concepts such as peptide-based vaccines, molecules based on biotechnological models such as recombinant allergens or DNA vaccines or considering the pathophysiological mechanism of the disease such as biologics or monoclonal antibodies which are currently under preclinical and/or clinical development [4,5].…”