Allergen-specific polyclonal antibodies reduce allergic disease in a mouse model of allergic asthma.
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.
Moerch
Ulrik
U
Symphogen A/S, Elektrovej, Lyngby, Denmark.
Haahr Hansen
Margit
M
Vest Hansen
Nils Jakob
NJ
Rasmussen
Lone Kjaer
LK
Oleksiewicz
Martin B
MB
Frandsen
Torben P
TP
Haurum
John S
JS
Bregenholt
Søren
S
D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006651:Histocytochemistry; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood; D007167:Immunotherapy / Q000379:methods* / Q000592:standards; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D000906:Antibodies; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D010047:Ovalbumin