Clinical use of adjuvants in allergen-immunotherapy

Abstract

Allergen-specific Immunotherapy (AIT) is the only available treatment aimed to tackle the underlying causes of allergy. The active components of subcutaneous vaccines traditionally consist of natural or modified allergen extracts which can be combined with adjuvant platforms. In recent years new targets have been further developed in an attempt to raise the safety and efficacy profile of AIT. Areas covered: In this review, we discuss the desirable attributes of adjuvants and delivery systems from empiricism to rational design, for current and future clinical applications in AIT. Expert commentary: The introduction of novel adjuvants, in combination with active targets, has been demonstrated to reduce symptoms of AIT, increase clinical efficacy of allergy treatment and reduce the number of doses. The evolution of vaccine development for AIT is entering a phase of scientific progress that challenges dogmas. Over the past century the traditional concept of immunotherapy, entailing long-course administration of native extract preparations and first generation adjuvants, has seen evolution in the past decade from proof-of-concept to clinical development pipelines encompassing the advent of second generation adjuvants and delivery systems forming essential components of modern AIT development.

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

“…[15][16][17] For long time, the main effects attributed to alum have been related to its depot effect leading to the slow release of the adsorbed allergens. 15,18 Alum also activates innate immune responses in DCs and macrophages. Alum induces the release of uric acid and double-stranded DNA, which activate NLRP3 inflammasome and IRF3 leading to the production of pro-inflammatory cytokines.…”

“…19,20 However, the detailed molecular mechanisms driving alum adjuvanticity still remain largely unknown. 15,18 Metabolic reprogramming in immune cells refers to the changes occurring after activation in the intracellular metabolic pathways that lead to functional regulation. 21 DCs' function is finely regulated by metabolic reprogramming in cooperation with immune pathways.…”

Adjuvants in Allergen-Specific Immunotherapy: Modulating and Enhancing the Immune Response

“…It should also promote an appropriate immune response [11]. Currently, the desired characteristics of the ideal adjuvant for AIT have been extended: it should also combine optimal physiochemical properties (eg, particle morphology and adsorption capacity) with biological activity properties (eg, enhancing IgG4 antibody titers and avoiding the T H 2-type immune response) [12]. In addition, the European Medicines Agency released a guideline on adjuvants in vaccines for human use; the quality and nonclinical (including toxicity) chapters are applicable to AIT [13].…”

Development of subcutaneous allergen immunotherapy (part 2): preventive aspects and innovations

“…By definition, an adjuvant is an excipient that enhances the effect of a drug without having a pharmacological effect of its own [38].…”

“…This treatment concept is also used in allergology [38]. The goal of using adjuvant molecules is to enhance the immunological and thus also the clinical efficacy of AIT [38].…”