Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance

Abstract

Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation, and reporting have developed significantly. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety, and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike. Those standards should be followed today, and products answering to them should be preferred over others lacking optimization and proof of efficacy and safety. Molecular and cellular mechanisms of AIT include early mast cell and basophil desensitization effects, regulation of T- and B-cell responses, regulation of IgE and IgG production, and inhibition of responses from eosinophils, mast cells, and basophils in the affected tissues. There were many developments to improve vaccination strategies, demonstration of new molecules involved in molecular mechanisms, and demonstration of new biomarkers for AIT during the last few years. The combination of probiotics, vitamins, and biological agents with AIT is highlighting current advances. Development of allergoids and recombinant and hypoallergenic vaccines to skew the immune response from IgE to IgG and regulation of dendritic cell, mast cell, basophil, innate lymphoid cell, T-cell, and B-cell responses to allergens are also discussed in detail.

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

“…It is widely accepted that the efficiency of allergen‐specific T‐cell responses during allergen immunotherapy correlates with the capability of this therapy for skewing DCs 39. We have shown that PM‐allergoids promote the generation of Th1 and Treg cells in vitro, but also in vivo upon subcutaneous immunization in mice 16.…”

Alum impairs tolerogenic properties induced by allergoid‐mannan conjugates inhibiting mTOR and metabolic reprogramming in human DCs

“…29,30 This is a paradigmatic study revealing the importance of the better understanding of the molecular mechanisms driving alum adjuvanticity in the context of allergy, especially in humans, to continue improving allergen vaccine formulations for AIT. Allergoid-mannan conjugates represent a major development in the search of novel vaccine approaches to improve AIT, 6,[9][10][11] and Alum was introduced as a vaccine adjuvant in 1926 by Glenny et al, 31 and since 1937, it is used in AIT. Although there are different adjuvant preparations that can be used in AIT as immunostimulants (ie, mineral salts or TLR-targeting adjuvants) or delivery systems (ie, different types of microand nanoparticles), 11 nowadays most of the subcutaneous vaccines for AIT include alum as adjuvant.…”

Recent developments and highlights in immune monitoring of allergen immunotherapy

“…Activated basophils are important biomarkers of allergic responses, reflecting specific IgE functional activity. In vitro basophil activation tests (BAT) may be useful in monitoring patients on AIT, by ex vivo measurements of CD63 or CD203c expression, basophil histamine release (BHR) or diamine oxidase (DAO), avoiding the risk of severe allergic reactions with in vivo allergen challenge . However, advances in practical aspects of the test are required for standardization and adaptation for use in routine laboratories.…”

“…Information that can be obtained from sequence analysis is highlighted vivo allergen challenge. [94][95][96][97] However, advances in practical aspects of the test are required for standardization and adaptation for use in routine laboratories. Due to their sequestration into tissues, mast cells remain difficult to investigate in the context of AIT and immune monitoring.…”