Is vaccination against IgE possible?
A substantial reduction in the levels of both total and antigen specific IgE will most likely result in improved symptom scores in atopic individuals. Based on this assumption we initiated a project to study the possibility of reducing levels of circulating and mast cell bound IgE, by inducing a strong autoimmune antibody response against IgE in the host. Bacterially produced fusion proteins containing constant domains two (CH2) and three (CH3) of rat IgE directly linked to the glutathione-S-transferase (GST) protein from Schistosoma japonicum or to the maltose binding protein of Esherichia coli were used as the active components of the allergy vaccine. Injection of either of these fusion proteins together with adjuvant led to the induction of a strong autoimmune anti-IgE response in several IgE low or medium responder strains of rats. Vaccination of ovalbumin sensitised Wistar rats with the GST-C2C3 fusion protein resulted in a profound decrease in serum IgE levels and later in a nearly complete block in histamine release from mast cells and basophils upon challenge with either a cross-linking polyclonal anti-IgE antiserum or a specific allergen. This shows that it is possible to reduce IgE levels in an animal to such an extent that it gives a clear clinical effect. Recent studies with an extended panel of rat strains including four IgE high responder strains, indicate that induction of the autoimmune response is dependent on the plasma concentration of IgE before vaccination. A high concentration of IgE has a negative effect on the induction of autoimmunity, most likely by inducing a B-cell tolerance in the host. Vaccinated subjects with very high IgE concentrations thereby responds poorly to the vaccine. Current studies are aimed at overcoming this potential limitation of the vaccination procedure.
Hellman
L
L
Department of Medical Immunology and Microbiology, University of Uppsala.
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D004396:Coloring Agents / Q000008:administration & dosage; D005070:Evans Blue / Q000008:administration & dosage; D005544:Forecasting; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D051381:Rats; D012867:Skin / Q000276:immunology; D014611:Vaccination
D004396:Coloring Agents; D007073:Immunoglobulin E; D005070:Evans Blue