Allergen immunotherapy: past, present and future

Abstract

Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites and the venom of stinging insects. The classical protocol, introduced in 1911, involves repeated subcutaneous injection of increasing amounts of allergen extract, followed by maintenance injections over a period of 3 years, achieving a form of allergen-specific tolerance that provides clinical benefit for years after its discontinuation. More recently, administration through the sublingual route has emerged as an effective, safe alternative. Oral immunotherapy for peanut allergy induces effective ‘desensitization’ but not long-term tolerance. Research and clinical trials over the past few decades have elucidated the mechanisms underlying immunotherapy-induced tolerance, involving a reduction of allergen-specific T helper 2 (T H 2) cells, an induction of regulatory T and B cells, and production of IgG and IgA ‘blocking’ antibodies. To better harness these mechanisms, novel strategies are being explored to achieve safer, effective, more convenient regimens and more durable long-term tolerance; these include alternative routes for current immunotherapy approaches, novel adjuvants, use of recombinant allergens (including hypoallergenic variants) and combination of allergens with immune modifiers or monoclonal antibodies targeting the T H 2 cell pathway.

Biological therapy practice, biomarkers of severe asthma and novel approaches for attaining immunomodulation in upper airway disease

“…The final Editor's Choice article evaluates the allergenicity and immunogenicity of a hybrid molecule containing T-cell epitopes from three major house dust mite allergens, Der p 1, Derp 2 and Der p 23, as a novel therapeutic option for allergen immunotherapy (AIT). 7 AIT is the only clinical management of allergies that can control the progression of these immune-mediated diseases by inducing immunological tolerance 8,9 Therapies with T-cell-targeted molecules can significantly impact the safety and efficacy of AIT, making them favourable alternatives to natural extracts.…”

“…The final Editor's Choice article evaluates the allergenicity and immunogenicity of a hybrid molecule containing T‐cell epitopes from three major house dust mite allergens, Der p 1, Derp 2 and Der p 23, as a novel therapeutic option for allergen immunotherapy (AIT) 7 . AIT is the only clinical management of allergies that can control the progression of these immune‐mediated diseases by inducing immunological tolerance 8,9 Therapies with T‐cell‐targeted molecules can significantly impact the safety and efficacy of AIT, making them favourable alternatives to natural extracts.3 A series of clinical trials have already demonstrated that hypoallergenic T‐cell epitope‐based allergens can compose safe and effective therapeutic formulations for AIT. This study aimed to generate a hypoallergenic hybrid molecule containing T‐cell epitopes from these three major allergens, Der p 1, Der p 2 and Der p 23.…”

Mechanisms and biomarkers of successful allergen-specific immunotherapy

“…AIT can be applied through multiple routes depending on the type of allergic disease and the source of sensitization [ 19 ]. Likewise, the selected application route leads to particularities in the antigen-presentation process, reflected in differences in efficacy and safety [ 20 ].…”

“…Subcutaneous immunotherapy (SCIT) is the oldest and most frequently used application route of AIT, which has been employed for more than a century [ 7 ]. SCIT is regarded as a safe and valid therapy for several allergic diseases including venom allergy, AR, and allergic asthma [ 19 ]. While adverse reactions occur in up to 71% of patients, severe side effects are rare [ 22 ].…”

“…FDA authorized the first OIT drug for treating peanut allergies in 2020 [ 26 ]. Unlike SLIT, the release of the allergen occurs in the digestive tract where there is a large amount of gut-associated lymphoid tissue [ 19 ].…”