PMID- 16699287 OWN - NLM STAT- MEDLINE DCOM- 20060713 LR - 20060613 IS - 1018-2438 (Print) IS - 1018-2438 (Linking) VI - 140 IP - 3 DP - 2006 TI - Allergen-specific polyclonal antibodies reduce allergic disease in a mouse model of allergic asthma. PG - 261-9 AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. FAU - Moerch, Ulrik AU - Moerch U AD - Symphogen A/S, Elektrovej, Lyngby, Denmark. FAU - Haahr Hansen, Margit AU - Haahr Hansen M FAU - Vest Hansen, Nils Jakob AU - Vest Hansen NJ FAU - Rasmussen, Lone Kjaer AU - Rasmussen LK FAU - Oleksiewicz, Martin B AU - Oleksiewicz MB FAU - Frandsen, Torben P AU - Frandsen TP FAU - Haurum, John S AU - Haurum JS FAU - Bregenholt, Soren AU - Bregenholt S LA - eng PT - Journal Article DEP - 20060511 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Antibodies) RN - 0 (Recombinant Proteins) RN - 37341-29-0 (Immunoglobulin E) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Administration, Intranasal MH - Animals MH - Antibodies/administration & dosage/immunology/*therapeutic use MH - Antibody Specificity MH - Asthma/*immunology/*therapy MH - Bronchoalveolar Lavage Fluid/cytology MH - Cell Count MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Histocytochemistry MH - Hypersensitivity, Immediate/immunology/prevention & control MH - Immunoglobulin E/blood MH - Immunotherapy/*methods/standards MH - Lung/immunology MH - Mice MH - Mice, Inbred BALB C MH - Ovalbumin/immunology MH - Recombinant Proteins/administration & dosage/therapeutic use EDAT- 2006/05/16 09:00 MHDA- 2006/07/14 09:00 CRDT- 2006/05/16 09:00 PHST- 2005/03/22 00:00 [received] PHST- 2006/01/10 00:00 [accepted] PHST- 2006/05/16 09:00 [pubmed] PHST- 2006/07/14 09:00 [medline] PHST- 2006/05/16 09:00 [entrez] AID - 93283 [pii] AID - 10.1159/000093283 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2006;140(3):261-9. doi: 10.1159/000093283. Epub 2006 May 11.