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 presensitized to the antigen. 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 utilized in AIT redirect the Th2 immune response towards 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.

中文翻译：

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过敏原免疫疗法中市售佐剂和配方的最新技术：欧洲过敏和临床免疫学学会 (EAACI) 的立场文件

自 100 多年前引入过敏原免疫疗法 (AIT) 以来，重点一直是过敏原提取物的标准化，其中可靠的过敏原分子组成受到最高关注。虽然佐剂在欧洲 AIT 中发挥着重要作用，但对它们的研究较少。在本意见书中，我们引用当前证据总结了 AIT 中当前未满足的佐剂需求。在欧洲销售的产品中使用四种佐剂：氢氧化铝 (Al(OH)3) 是最常用的佐剂，微晶酪氨酸 (MCT)、单磷酰脂质 A (MPLA) 和磷酸钙 (CaP) 使用较少。最近对人类和使用小鼠模型的研究部分表征了佐剂对预先存在的免疫反应的作用机制。AIT 不同于激发对传染原免疫的预防性疫苗，因为在过敏症中，患者对抗原预先敏感。佐剂的预期作用方式是同时增强过敏原的免疫原性，同时在注射部位沉淀过敏原以降低过敏反应的风险。用不同的佐剂观察到对比的免疫效果。氢氧化铝最初会增强 Th2 反应，而 AIT 中使用的其他佐剂将 Th2 免疫反应重定向到 Th1 免疫。在不同的时间长度后，每种佐剂都支持耐受性。对佐剂作用机制的进一步研究可能会建议比目前的三到五年方案更短的治疗期，从而提高患者的依从性。