Department of Otorhinolaryngology, University Hospital Mannheim, Center for Rhinology and Allergology, Wiesbaden, Germany.
Int Arch Allergy Immunol. 2011;154(4):336-44. doi: 10.1159/000321826. Epub 2010 Oct 25.
Sublingual immunotherapy (SLIT) allergy vaccines have an excellent safety profile, but opinions vary on their efficacy, and treatment regimens are often lengthy. This study assessed the effects of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPL®) on safety/tolerability and clinical and immunological efficacy when combined with grass pollen SLIT formulations in treating patients with seasonal allergic rhinitis. This is the first reported study of adjuvanted SLIT.
In this double-blind placebo-controlled phase I/IIa study, 80 grass pollen-sensitive subjects were randomized into 4 groups of 20 subjects to receive daily treatment for 8 weeks. Sixteen patients per group received SLIT and 4 received placebo. The formulation given to each group varied with respect to grass pollen extract and MPL content. Grass allergen nasal challenge tests (NCTs) were performed prior to dosing and in weeks 4 and 10. Grass pollen-specific immunoglobulin G (IgG) and IgE antibodies were measured at baseline and prior to dosing in weeks 2, 3, 4, 5 and 10.
Local and systemic adverse events were generally comparable for patients who received active treatment and placebo. Patients in the 2 groups given SLIT containing the highest amount of MPL experienced the highest proportion of negative NCTs after 10 weeks (47 and 44%, vs. 20% with placebo). These patients also showed earlier median increases in specific IgG and smaller increases in IgE levels than those receiving other formulations.
These results suggest that SLIT preparations containing MPL are well tolerated and alter the immunological response to grass antigens after 3 weeks of exposure, with an associated suppression of nasal challenge responses.
舌下免疫疗法（SLIT）过敏疫苗具有极佳的安全性，但对其疗效的看法不一，且治疗方案往往较长。本研究评估了 Toll 样受体 4 激动剂单磷酰脂质 A（MPL®）与草花粉 SLIT 制剂联合使用治疗季节性变应性鼻炎患者时的安全性/耐受性以及临床和免疫疗效。这是首例报道的佐剂 SLIT 研究。
在这项双盲安慰剂对照的 I/IIa 期研究中，80 名对草花粉敏感的受试者被随机分为 4 组，每组 20 名，每天接受治疗 8 周。每组中有 16 名患者接受 SLIT，4 名患者接受安慰剂。每组给予的配方因草花粉提取物和 MPL 含量而异。在给药前和第 4 周和第 10 周进行草过敏原鼻挑战测试（NCT）。在基线和第 2、3、4、5 和 10 周给药前测量草花粉特异性免疫球蛋白 G（IgG）和 IgE 抗体。
接受活性治疗和安慰剂的患者的局部和全身不良事件通常相似。接受含有最高量 MPL 的 SLIT 的 2 组患者在 10 周后经历了最高比例的阴性 NCT（47%和 44%，而安慰剂组为 20%）。这些患者还表现出比接受其他配方的患者更早的特异性 IgG 中位数增加和 IgE 水平增加较小。
这些结果表明，含有 MPL 的 SLIT 制剂具有良好的耐受性，并在暴露 3 周后改变对草抗原的免疫反应，伴随鼻挑战反应的抑制。
