University of Adelaide, North Terrace, Adelaide, Australia; Royal Adelaide Hospital, North Terrace, Adelaide, Australia; Flinders University, Bedford Park, Australia.
Allergy and Clinical Immunology Department, Flinders Medical Centre, Bedford Park, Australia.
J Allergy Clin Immunol. 2019 Aug;144(2):504-513.e16. doi: 10.1016/j.jaci.2019.03.035. Epub 2019 Jul 9.
Allergic reactions to Hymenoptera insect stings remain a major global clinical problem. Although effective, parenteral desensitization regimens require use of costly venom extracts and require frequent visits over extended periods of time.
Adjuvants are commonly used to enhance the efficacy of infectious disease vaccines, and this study asked whether Advax (Vaxine Pty Ltd, Adelaide, Australia), a novel noninflammatory polysaccharide adjuvant, might provide similar benefits for allergy desensitization.
A randomized, controlled phase 1/2 trial was undertaken in 27 adults with a history of rapid-onset systemic allergic reactions to honeybee stings and positive specific IgE levels to evaluate the safety and efficacy of honeybee venom immunotherapy (HBVIT) combined with Advax adjuvant. Venom immunotherapy (VIT) was administered monthly for 30 months after achievement of maintenance doses.
Advax-adjuvanted HBVIT was well tolerated. Around week 14 of VIT, specific IgG responses peaked in both groups but increased earlier, peaked higher, and were better maintained through the end of the study in the Advax-adjuvanted arm. Several different patterns of serologic response to VIT were seen; some subjects had a dominant IgG response, some had a combined IgG and IgG response, and some had an exclusively IgG response. In some subjects specific IgE levels increased during the induction phase and then decreased, whereas in others specific IgE levels progressively decreased from the start of VIT.
Advax adjuvant favorably enhanced the immunogenicity of HBVIT, with an early and prolonged switch to specific IgG production. The ability of Advax adjuvant to enhance VIT efficacy warrants further study.
蜂类昆虫蜇刺引起的过敏反应仍然是一个全球性的临床重大问题。虽然有效，但皮下免疫脱敏方案需要使用昂贵的毒液提取物，并且需要在很长一段时间内频繁就诊。
佐剂常用于增强传染病疫苗的效果，本研究旨在探讨一种新型非炎症性多糖佐剂 Advax（Vaxine Pty Ltd，澳大利亚阿德莱德）是否也能为过敏脱敏带来类似的益处。
一项随机、对照的 1/2 期试验在 27 名有快速发作的全身性蜂蜇过敏反应史且对蜜蜂毒液特异性 IgE 水平阳性的成年人中进行，以评估蜜蜂毒液免疫疗法（HBVIT）联合 Advax 佐剂的安全性和有效性。在达到维持剂量后，每月进行 30 个月的毒液免疫治疗（VIT）。
Advax 佐剂的 HBVIT 耐受性良好。在 VIT 治疗约 14 周时，两组的特异性 IgG 反应均达到峰值，但在 Advax 佐剂组更早、峰值更高，并在研究结束时保持更好。在 VIT 治疗中观察到几种不同的血清学反应模式；一些受试者有主导的 IgG 反应，一些有 IgG 和 IgG 联合反应，一些仅有 IgG 反应。在一些受试者中，特异性 IgE 水平在诱导期增加，然后下降，而在另一些受试者中，特异性 IgE 水平从 VIT 开始就逐渐下降。
Advax 佐剂有利地增强了 HBVIT 的免疫原性，早期和长期转换为特异性 IgG 产生。Advax 佐剂增强 VIT 疗效的能力值得进一步研究。
