BACKGROUND BM32, a grass pollen allergy vaccine containing four recombinant fusion proteins consisting of hepatitis B-derived PreS and hypoallergenic peptides from the major timothy grass pollen allergens adsorbed on aluminium hydroxide has been shown to be safe and to improve clinical symptoms of grass pollen allergy upon allergen-specific immunotherapy (AIT). We have investigated the immune responses in patients from a two years double-blind, placebo-controlled AIT field trial with BM32. METHODS Blood samples from patients treated with BM32 (n = 27) or placebo (Aluminium hydroxide) (n = 13) were obtained to study the effects of vaccination and natural allergen exposure on allergen-specific antibody, T cell and cytokine responses. Allergen-specific IgE, IgG, IgG1 and IgG4 levels were determined by ImmunoCAP and ELISA, respectively. Allergen-specific lymphocyte proliferation by 3H thymidine incorporation and multiple cytokine responses with a human 17-plex cytokine assay were studied in cultured peripheral blood mononuclear cells (PBMCs). FINDINGS Two years AIT comprising two courses of 3 pre-seasonal injections of BM32 and a single booster after the first pollen season induced a continuously increasing (year 2 > year 1) allergen-specific IgG4 response without boosting allergen-specific IgE responses. Specific IgG4 responses were accompanied by low stimulation of allergen-specific PBMC responses. Increases of allergen-specific pro-inflammatory cytokine responses were absent. The rise of allergen-specific IgE induced by seasonal grass pollen exposure was partially blunted in BM32-treated patients. INTERPRETATION AIT with BM32 is characterised by the induction of a non-inflammatory, continuously increasing allergen-specific IgG4 response (year 2 > year1) which may explain that clinical efficacy was higher in year 2 than in year 1. The good safety profile of BM32 may be explained by lack of IgE reactivity and low stimulation of allergen-specific T cell and cytokine responses. FUNDINGS Grants F4605, F4613 and DK 1248-B13 of the Austrian Science Fund (FWF).

中文翻译：

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两年的重组草花粉过敏疫苗 BM32 治疗诱导了持续增加的过敏原特异性 IgG4 反应。

背景 BM32是一种草花粉过敏疫苗，含有四种重组融合蛋白，由乙型肝炎衍生的PreS和吸附在氢氧化铝上的主要梯牧草花粉过敏原的低过敏性肽组成，已被证明是安全的，并且可以改善草花粉过敏的临床症状。过敏原特异性免疫疗法（AIT）。我们研究了为期两年的双盲、安慰剂对照的 BM32 AIT 现场试验患者的免疫反应。方法 获得接受 BM32（n = 27）或安慰剂（氢氧化铝）（n = 13）治疗的患者的血液样本，以研究疫苗接种和天然过敏原暴露对过敏原特异性抗体、T 细胞和细胞因子反应的影响。过敏原特异性 IgE、IgG、IgG1 和 IgG4 水平分别通过 ImmunoCAP 和 ELISA 测定。在培养的外周血单核细胞 (PBMC) 中研究了通过 3H 胸苷掺入的过敏原特异性淋巴细胞增殖和人类 17 重细胞因子测定的多种细胞因子反应。结果 两年 AIT 包括两个疗程的 3 次季节性前注射 BM32 和第一个花粉季节后的单次加强剂，诱导持续增加（第 2 年 > 第 1 年）过敏原特异性 IgG4 反应，而不会增加过敏原特异性 IgE 反应。特异性 IgG4 反应伴随着过敏原特异性 PBMC 反应的低刺激。过敏原特异性促炎细胞因子反应没有增加。在接受 BM32 治疗的患者中，季节性草花粉暴露引起的过敏原特异性 IgE 升高部分减弱。解释 AIT 与 BM32 的特点是诱导非炎症性、持续增加的过敏原特异性 IgG4 反应（第 2 年 > 第 1 年），这可以解释第 2 年的临床疗效高于第 1 年。BM32 的良好安全性可能是由于缺乏 IgE 反应性和过敏原特异性 T 细胞和细胞因子反应的低刺激。资助奥地利科学基金 (FWF) 的 F4605、F4613 和 DK 1248-B13。