Immunization with purified natural and recombinant allergens induces mouse IgG1 antibodies that recognize similar epitopes as human IgE and inhibit the human IgE-allergen interaction and allergen-induced basophil degranulation.
Molecular characterization of allergens by recombinant DNA technology has made rapid progress in the recent few years. In the present study we immunized mice with aluminum hydroxide-adsorbed purified recombinant major timothy grass pollen allergens (rPhl p 1, rPhl p 2, rPhl p 5), dog albumin, a major animal dander allergen, and proteins with low (beta-lactoglobulin) or no (ribulose diphosphate carboxylase) allergenic potential in humans. Allergens that bind high levels of IgE in humans (Phl p 1, Phl p 5, dog albumin) induced high IgE and IgG1 levels in mice, whereas proteins with little or no allergenic activity in humans failed to induce significant IgE and IgG1 levels in mice. Continuous immunization for a period of 27 wk resulted in the production of mouse IgG1 Abs that recognized recombinant allergen fragments/epitopes defined by IgE Abs of allergic patients. As a consequence, allergen-specific mouse Abs strongly inhibited human IgE binding to the allergens and suppressed the allergen-induced histamine release from human basophils. In summary, our data indicate that 1) the allergenic potency of a protein may be related to its overall immunogenicity and 2) prolonged immunization with single purified recombinant allergens induces protective IgG Abs. The presented experimental in vivo/in vitro system allows the evaluation of Ag preparations (e.g., recombinant allergens) to be used for immunotherapy in humans.
Vrtala
S
S
Institute of General and Experimental Pathology, Department of Internal Medicine I, AKH (Vienna General Hospital), University of Vienna, Austria.
Ball
T
T
Spitzauer
S
S
Pandjaitan
B
B
Suphioglu
C
C
Knox
B
B
Sperr
W R
WR
Valent
P
P
Kraft
D
D
Valenta
R
R
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology*; D003888:Desensitization, Immunologic; D004285:Dogs; D018604:Epitope Mapping; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C048844:anti-IgG; D007073:Immunoglobulin E