Unit of Pediatric Allergy and Pneumology, Hospital Universitari i Politècnic la Fe, Valencia, Spain.
Department of Allergy, Hospital Universitari i Politècnic la Fe, Valencia, Spain.
Allergy. 2022 Oct;77(10):3096-3107. doi: 10.1111/all.15374. Epub 2022 May 27.
Polymerized allergens conjugated to non-oxidized mannan (PM-allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM-allergoids are readily taken up by DCs and induce Treg cells. This first-in-human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM-allergoid (PM-HDM) administered subcutaneously (SC) or sublingually (SL).
In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannan-conjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers.
No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups.
PM-HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.
与非氧化甘露聚糖偶联的聚合过敏原（PM 类原）是针对树突状细胞（DC）的新型疫苗。先前的实验数据表明，PM 类原可被 DC 有效摄取，并诱导 Treg 细胞。这项首次在人体中进行的研究旨在评估安全性，并确定皮下（SC）或舌下（SL）给药的屋尘螨 PM 类原（PM-HDM）的最佳剂量。
在一项随机、双盲、双模拟、安慰剂对照试验中，196 名受试者按 9 个给药组分别接受安慰剂或 PM-HDM，剂量分别为 500、1000、3000 或 5000 个甘露聚糖结合治疗单位（mTU）/mL，持续 4 个月。所有受试者均接受了 5 次 SC 剂量（每次 0.5ml），每 30 天一次，同时每天接受 0.2ml 的 SL 治疗。主要疗效终点是在基线和研究结束时用 D. pteronyssinus 进行的滴定鼻激发试验（NPT）的改善。记录并评估所有不良事件和反应。次要终点是症状和药物评分（CSMS）和血清学标志物的组合。
未报告中度或重度不良反应。治疗后 NPT 改善的受试者在 SC 组中的比例为 45%至 62%，在 SL 组中的比例为 44%至 61%，在安慰剂组中的比例为 16%。在 500 mTU 以上，安慰剂组和活性组之间的统计学差异均有显著性，其中 SL 组 3000 mTU（p=0.004）和 SC 组 5000 mTU（p=0.011）的差异最高。与安慰剂相比，在 3000 mTU SC 组中 CSMS 改善达到 70%（p<0.001），在 5000 mTU SL 组中达到 40%（p=0.015）。
PM-HDM 免疫疗法在 SC 和 SL 中以 3000 或 5000 mTU/ml 的剂量进行时安全有效，可实现主要和次要临床终点。
