Sublingual Allergen Immunotherapy: Immunological Mechanisms and Prospects for Refined Vaccine Preparations

Abstract

Allergic diseases constitute a major health issue worldwide. Mainstay treatment constitutes allergen avoidance and pharmacotherapy for symptom relief, but allergen immunotherapy offers advantages of specific treatment with long lasting efficacy, and being able to modify the course of the disease. Conventional immunotherapy involves the subcutaneous injection of gradually increasing amounts of allergen extract but the use of current whole allergen extracts is restricted by the risk of adverse IgE-mediated events especially for potent allergens such as peanut and latex and for asthmatics. This has lead to interest in alternative routes of immunotherapy. Oral tolerance is a well-documented immune process and the sublingual route of administration of allergen immunotherapy is attracting interest. Recent meta-analyses show that sublingual allergen immunotherapy for grass pollen and house dust mite allergy is clinically effective and safer than injection immunotherapy. Some studies show SLIT induces changes of T cell anergy, immune deviation, blocking antibodies, and induction of regulatory T cells, as described for injection immunotherapy pointing to the need to target allergen-specific T cells, there is emergent evidence that the oral mucosa presents distinct regulatory features. Evidence suggests that oral dendritic cells play a key role in inducing tolerance especially when allergen is taken up via Fc receptor bound IgE. This suggests that although both would target allergen-specific T cells, allergen formulations may differ with respect to IgE epitopes for optimal SLIT compared with SCIT. Identification of the molecular nature of the allergen-DC receptor interaction is required to determine whether short peptides or recombinant allergen preparations and of suitable adjuvants specifically tailored for the sublingual route will allow the development of improved allergen formulations and delivery strategies for efficacy of treatment whilst decreasing IgE-mediated adverse effects.

Ara h 2 peptides containing dominant CD4+ T-cell epitopes: Candidates for a peanut allergy therapeutic

“…Specific immunotherapy is also accompanied by decreased specific IgE, increased protective specific IgG 4 antibody levels, and reduced number and activation of mast cells, eosinophils, and basophils. [17][18][19][20][21][22] Stimulation of appropriate T-cell responses during allergen-specific immunotherapy is necessary for effective desensitization. 22 Conventional immunotherapy administers whole allergen extracts, but peptides containing T-cell epitopes of major allergens provide an effective, safer (non-IgE-reactive) alternative.…”

Clinical and Immunologic Effects of Allergen-Specific Sublingual Immunotherapy in a Canine Model of Atopic Dermatitis: A Double Blind, Randomized, Controlled Study

“…The idea behind SLIT is that the allergen is captured within the oral mucosa by Langerhanslike dendritic cells expressing high-affinity IgE receptors, producing IL-10 and TGF-β [38]. The oral mucosa has a restricted number of proinflammatory cells, such as mast cells, and that contributes to the safety of SLIT [39]. Thus for our study we decided to investigate the effects on IL-10 and TGF-β as they are T regulatory dependent cytokines shown to be important in successful SLIT [40][41][42].…”

Strategies of mucosal immunotherapy for allergic diseases

“…131 The clinical trial results for tracheal administration have suggested that clinical efficacy is unproven and that the risk/benefit ratio is unfavorable. 132,133 SLIT The mechanisms behind SLIT include the production of blocking IgG4 antibodies, 134,135 the presence of high numbers of tolerogenic DC subsets, the induction of regulatory T cells, 136,137 and the programming of the immune system toward a regulatory state of unresponsiveness to specific allergens. SLIT may also increase IL-10, which has a clear role in suppressing allergic immune responses.…”