Allergen extracts are used to diagnose and treat allergic disease. This program is aimed toward improving the safety and efficacy of allergen extracts in the US. Specific areas of interest include cockroach allergen extracts; the endotoxin content of standardized allergen extracts; the development of specific antibodies to allergens for the purpose of improved standardization; and the development of IgE combinatorial libraries for specific allergens. To support its ongoing monitoring program of therapeutic and diagnostic allergen preparations, LIB has initiated a multifaceted study of the factors that enhance or diminish the immune responses to allergens. These include: 1. Lipopolysaccharide (LPS) effect on allergen responses. LPS is a common contaminant in latex gloves and in the environment. LPS is also present in many allergen vaccines. In previous work, Dr. Slater has demonstrated that LPS increases murine IgG and IgE responses to recombinant Hev b 5, that this effect can be observed with ovalbumin as well, and that the effect is enhanced by lower airway delivery of the allergen and LPS. Current work is focused on two areas of interest. Ms. Valerio is examining the cytokine specificity of the LPS-allergen responses, and will identify the anatomic localization of the murine airway responses to LPS. We are also measuring the endotoxin content of commercial allergen vaccines, and will determine the effect of the endotoxin in these vaccines on murine responses to allergen injection. 2. Allergen vaccines are the most commonly utilized reagents for immunotherapy, and the standardization of allergens is an important step in ensuring the safety and efficacy of allergens for immunotherapy. Dr. Slater and Ms. Valerio have initiated work on the standardization of cockroach allergens in the US. In initial work, LIB has demonstrated that currently available cockroach allergen vaccines are highly variable in their protein and allergen content. 3. Construction of a combinatorial library for cockroach allergen antibodies. The study of cockroach allergens requires an analysis of the immunodominant proteins within a highly complex mixture. Dr. Finlay is using recombinant DNA technology to construct a library of human antibodies to cockroach. This technology will allow us to identify and study relevant allergens. Dr. deVore is also studying animal (chicken and rabbit) antibodies directed to common allergens.

Agency
National Institute of Health (NIH)
Institute
Center for Biologics Evaluation and Research - Bactrial Products (CBERBP)
Type
Intramural Research (Z01)
Project #
1Z01BJ008007-06
Application #
6839035
Study Section
(LAIB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2003
Total Cost
Indirect Cost