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    Allergy. 2019 Nov 27. doi: 10.1111/all.14134
    State-of-the-art in marketed adjuvants and formulations in Allergen Immunotherapy: a position paper of the European Academy of Allergy and Clinical Immunology (EAACI).
    Jensen-Jarolim E1,  Bachmann M2,  Bonini S3,  Jacobsen L4,  Jutel M5,  Klimek L6,  Mahler V7,  Mösges R8,  Moingeon P9,  O Hehir RE10,  Palomares O11,  Pfaar O12,  Renz H13,  Rhyner C14,  Roth-Walter F15,  Rudenko M16,  Savolainen J17,  Schmidt-Weber C18,  Traidl-Hoffmann C19,  Kündig T20
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    Abstract

    Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre-existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is pre-sensitized to the allergen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilised in AIT redirect the Th2 immune response toward Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three-to-five-year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.


    © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

    KEYWORDS: Adjuvants, allergen immunotherapy; aluminium, microcrystalline tyrosine, monophosphoryl-lipid A (MPLA)

    Publikations ID: 31774179
    Quelle: öffnen
     
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