The development of a therapeutic vaccine for Type 1 allergy is proposed that will elicit isotype specific anti-IgE that results in desensitization regardless of allergen. The vaccine, comprised of synthetic peptide immunogens that mimic two unique sites on IgE, will elicit antibodies with specificities for (1) an exposed portion of the anchor sequence of membrane-bound IgE on IgE secreting B cells, and (2) a site on the C4 domain of IgE that is also implicated in IgE-secretion as well as in the triggering of mast cells and basophils. For Phase I pilot study, immunostimulatory IgE peptide immunogens will be synthesized by proprietary technology and administered to mice using a pharmaceutically acceptable adjuvant. Readily measurable effects for both component immunogens of this immunotherapy are expected to be evocation of site- specific IgG against IgE and reduction of IgE response. Accordingly, feasibility for immunotherapy will be demonstrated in mice by (1) the elicitation of site-specific autoantibodies that (2) affect reversible isotype-specific suppression of IgE production and prevent sensitization, and, (3) do not result in immunopathology or other adverse effects. The site-specific anti-IgE will not crosslink IgE and stimulate histamine release by human basophils.Proposed commercial application:The intended product is an immunotherapy for the alleviation allergic diseases. It is predicted to be highly effective because its mode of action, i.e., directed at IgE rather than the allergen, will result in desensitization with no need to identify and formulate specific allergens for each patient. It will be appropriate for all segments of the allergy market because of convenient administration and because its effects will be safe and reversible.National Institute of Allergy and Infectious Diseases (NIAID)
