Moerch Ulrik, Haahr Hansen Margit, Vest Hansen Nils Jakob, Rasmussen Lone Kjaer, Oleksiewicz Martin B, Frandsen Torben P, Haurum John S, Bregenholt Søren
Symphogen A/S, Elektrovej, Lyngby, Denmark.
Int Arch Allergy Immunol. 2006;140(3):261-9. doi: 10.1159/000093283. Epub 2006 May 11.
Recombinant allergen-specific immunoglobulin G (IgG) antibody therapy can reduce allergic asthma symptoms by inhibiting the immunoglobulin E (IgE)-mediated allergic response. This study investigated the effect of intranasally administered allergen-specific monoclonal (mAb) and polyclonal (pAb) antibody on airway inflammation and hyperresponsiveness (AHR) in a mouse model of human asthma.
Ovalbumin (OVA)-specific IgG2b antibodies were generated by phage display using spleens from OVA-immunized mice, and screening against OVA and finally expressed in CHO cells. Sensitized mice were treated intranasally with either a recombinant anti-OVA mAb (gc32) or a polyclonal preparation comprising seven selected antibodies (including gc32). Control mice received diluent only, OVA only, a control polymeric IgG or dexamethasone. Following challenge with nebulized OVA, investigators assessed airway inflammation by histology and cellular composition of the bronchoalveolar fluid, and methacholine-induced airway hyperresponsiveness (AHR). Serum levels of total and OVA-specific IgE were measured by ELISA.
Sensitized mice developed airway inflammation and AHR in response to OVA challenge. Intranasally administered OVA-specific murine polyclonal or monoclonal IgG2b antibodies both reduced OVA-induced lung inflammation. Polyclonal, but not anti-OVA mAb, also reduced AHR and eosinophil influx into the airway lumen. Both anti-OVA antibody preparations reduced levels of specific IgE with no effect on total IgE levels.
Intranasal treatment with allergen-specific pAb reduces pulmonary inflammation and AHR in a mouse model of allergic asthma, but allergen-specific mAb reduces inflammation only. Allergen-specific recombinant pAb offers a potentially valuable therapeutic approach to the management of allergic asthma.
重组变应原特异性免疫球蛋白G（IgG）抗体疗法可通过抑制免疫球蛋白E（IgE）介导的过敏反应来减轻过敏性哮喘症状。本研究在人类哮喘小鼠模型中，调查了经鼻给予变应原特异性单克隆（mAb）和多克隆（pAb）抗体对气道炎症和高反应性（AHR）的影响。
使用来自经卵清蛋白（OVA）免疫小鼠的脾脏，通过噬菌体展示产生OVA特异性IgG2b抗体，并针对OVA进行筛选，最终在CHO细胞中表达。致敏小鼠经鼻给予重组抗OVA单克隆抗体（gc32）或包含七种选定抗体（包括gc32）的多克隆制剂。对照小鼠仅接受稀释剂、仅接受OVA、对照聚合IgG或地塞米松。在用雾化OVA激发后，研究人员通过组织学和支气管肺泡灌洗液的细胞组成评估气道炎症，以及通过乙酰甲胆碱诱导的气道高反应性（AHR）。通过酶联免疫吸附测定法（ELISA）测量血清中总IgE和OVA特异性IgE的水平。
致敏小鼠在OVA激发后出现气道炎症和AHR。经鼻给予OVA特异性鼠多克隆或单克隆IgG2b抗体均减轻了OVA诱导的肺部炎症。多克隆抗体（而非抗OVA单克隆抗体）还降低了AHR以及嗜酸性粒细胞流入气道腔。两种抗OVA抗体制剂均降低了特异性IgE水平，而对总IgE水平无影响。
在过敏性哮喘小鼠模型中，经鼻用变应原特异性多克隆抗体治疗可减轻肺部炎症和AHR，但变应原特异性单克隆抗体仅减轻炎症。变应原特异性重组多克隆抗体为过敏性哮喘的治疗提供了一种潜在有价值的治疗方法。
