Faculty of Pharmacy, Department of Pharmaceutical Biology, University of Ljubljana, Aškerčeva 7, SI-1000, Ljubljana, Slovenia.
Clin Rev Allergy Immunol. 2020 Jun;58(3):326-341. doi: 10.1007/s12016-019-08752-x.
Bee venom immunotherapy is the main treatment option for bee sting allergy. Its major limitations are the high percentage of allergic side effects and long duration, which are driving the development of novel therapeutic modalities. Three general approaches have been evaluated including the use of hypoallergenic allergen derivatives, adjunctive therapy, and alternative delivery routes. This article reviews preclinical and clinical evidence on the therapeutic potential of these new therapies. Among hypoallergenic derivatives, hybrid allergens showed a markedly reduced IgE reactivity in mouse models. Whether they will offer therapeutic benefit over extract, it is still not known since clinical trials have not been carried out yet. T cell epitope peptides have proven effective in small clinical trials. Major histocompatibility complex class II restriction was circumvented by using long overlapping or promiscuous T cell epitope peptides. However, the T cell-mediated late-phase adverse events have been reported with both short and longer peptides. Application of mimotopes could potentially overcome both T cell- and IgE-mediated adverse events. During this evolution of vaccine, there has been a gain in safety. The efficacy was further improved with the use of Toll-like receptor-activating adjuvants and delivery systems. In murine models, the association of allergen Api m 1 with cytosine-guanosine rich oligonucleotides stimulated strong T-helper type-1 response, whereas its encapsulation into microbubbles protected mice against allergen challenge. An intralymphatic administration of low-dose vaccine has shown the potential to decrease treatment from 5 years to only 12 weeks. Bigger clinical trials are needed to follow up on these results.
蜂毒免疫疗法是治疗蜂蜇过敏的主要选择。其主要局限性是过敏副作用的高比例和长时间，这推动了新治疗方法的发展。已经评估了三种一般方法，包括使用低变应原性过敏原衍生物、辅助治疗和替代给药途径。本文综述了这些新疗法的治疗潜力的临床前和临床证据。在低变应原性衍生物中，杂交过敏原在小鼠模型中表现出明显降低的 IgE 反应性。它们是否会比提取物提供治疗益处尚不清楚，因为尚未进行临床试验。T 细胞表位肽已在小型临床试验中证明有效。通过使用长重叠或混杂 T 细胞表位肽绕过了主要组织相容性复合体 II 限制。然而，已经报道了使用短肽和更长肽都与 T 细胞介导的迟发性不良事件有关。模拟表位的应用有可能克服 T 细胞和 IgE 介导的不良事件。在疫苗的演变过程中，安全性得到了提高。使用 Toll 样受体激活佐剂和给药系统进一步提高了疗效。在小鼠模型中，与富含胞嘧啶-鸟嘌呤的寡核苷酸结合的过敏原 Api m 1 刺激了强烈的 T 辅助型 1 反应，而将其封装入微泡中则保护了小鼠免受过敏原的挑战。低剂量疫苗的淋巴管内给药显示出减少 5 年治疗时间至仅 12 周的潜力。需要更大的临床试验来跟进这些结果。
