Allergen-specific polyclonal antibodies reduce allergic disease in a mouse model of allergic asthma

• Published in: International Archives of Allergy and Immunology Vol. 140; no. 3; pp. 261 - 269
• Main Authors: Moerch, Ulrik, Haahr Hansen, Margit, Vest Hansen, Nils Jakob, Rasmussen, Lone Kjaer, Oleksiewicz, Martin B, Frandsen, Torben P, Haurum, John S, Bregenholt, Søren
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2006
• Subjects: Administration, Intranasal; Animals; Antibodies - administration & dosage; Antibodies - immunology; Antibodies - therapeutic use; Antibody Specificity; Asthma - immunology; Asthma - therapy; Bronchoalveolar Lavage Fluid - cytology; Cell Count; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Histocytochemistry; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - prevention & control; Immunoglobulin E - blood; Immunotherapy - methods; Immunotherapy - standards; Lung - immunology; Mice; Mice, Inbred BALB C; Ovalbumin - immunology; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use
• ISSN: 1018-2438; 1365-2567
• DOI: 10.1159/000093283

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.