SBIR-STTR Award

Allergic rhinitis affects 20% of the population in the USA and has a serious financial impact in both lost time and medical costs for physician visits and medication. Currently, treatment falls into three categories. The first is to identify the allergen and develop a strategy of avoidance by the patient. The second strategy is the use of pharmacological agents to prevent symptoms and the third approach is desensitization to a specific allergen. The most cost-effective strategy is that of allergen avoidance and hence, there is substantial benefit for reliable assays that can detect the allergen to which a patient is sensitive. Because skin testing is unpleasant for the patient and requires significant physician involvement, radioallergosorbent tests (RAST) are the optimal strategy to identify allergic reactivities in atopic individuals. The focus of this proposal is to improve the sensitivity of automated in vitro testing for allergens by replacing an expensive detection reagent, a specific antibody to human epsilon heavy chains, with a low-cost high affinity bacterial IgE binding protein. The reagent will improve sensitivity and reduce false negative results for a key screening test to identify the causative agent of allergic responses in atopic individuals. PROPOSED COMMERCIAL APPLICATION: The commercial application of the technology is to replace an anti-IgE antibody with a higher affinity specific bacterial protein. This product will find applications in diagnostic allergy testing and may provide new strategies for developing a novel therapeutic to prevent allergic reactions in atopic patients.

In the Phase I study we successfully identified a bacterial binding protein that bound selectively to human IgE in a non-immune manner. This purified binding protein has the potential to act as a tracer for human IgE without interference from other human plasma proteins like lgG, IgM or albumin that are present in large molar excess. The bacterial protein can capture human lgE when immobilized and can be biotinylated without loss of functional activity. These properties suggest that this protein can act as a protein A or protein G equivalent bacterial-binding protein for IgE. This bacterial protein has the potential to replace current second antibody reagents specific for the epsilon heavy chains that are currently used for allergy testing in clinical laboratories. There are many advantages of the bacterial tracer over the current antibody reagents that include ease of preparation, ability to readily modulate affinity and the economics of production. The Phase II proposal is designed to further characterize the bacterial IgE-binding activity and develop efficient expression and purification protocols for the wild type protein and finally, optimize the use of the IgE-binding protein in selected assays for total and allergen specific lgE. PROPOSED COMMERCIAL APPLICATION: Allergic rhinitis has been estimated to lead to 10 million physician office visits/year in the U.S. The total cost of allergic rhinitis in 1994 was estimated at $1.23 billion in lost productivity. In 1993 the cost for physicians visits and over the counter and prescription medications was estimated at $2.4 billion. Allergy testing, in the clinical laboratory, represents a major market. Laboratory assays to detect IgE response to specific allergens with increased sensitivity and reduced false negative results would be advantageous.

Public Health Relevance:
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Thesaurus Terms:
Bacterial Protein, Binding Protein, Diagnosis Design /Evaluation, Immunoglobulin E, Immunologic Assay /Test Allergen, Antibody Titering, Binding Site, Hypersensitivity, Immunology, Protein Protein Interaction, Reagent /Indicator, Rhinitis Clinical Research, Enzyme Linked Immunosorbent Assay, Human Tissue, Protein Purification