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Abstract

Grant Number:	1R43AI054075-01
PI Name:	CHEN, SWEY-SHEN A.
PI Email:	alexchen@iget-breathe.com
PI Title:
Project Title:	Allergy Protection by Active IgE B Cell Vaccines

Abstract: DESCRIPTION (provided by applicant): IgE-mediated allergic asthma, rhinitis, food allergy, atopic dermatitis, anaphylaxis cost annual 18 billions in medical costs and loss of productivity in this country. Regulation of IgE production by B cells is orchestrated by Th2 cytokines, and cognate interactions of B cells and Th2. IL-4 contributes to IgE production by skewing Th2 development. In animal model, our early studies demonstrated that IgE production can be down-regulated by IgE immunization. This prompts the product concept that human IgE B cell epitopes may be employed as protective vaccines for generating anti-lgE, which subsequently removes circulating human IgE. Indeed phase III clinical trial showed that humanized MAb, anti-IgE administered to asthmatic patients reduces levels of circulating IgE and alleviates allergic symptoms. It is critically important to raise antibodies against IgE B cell epitopes that block IgE binding to high affinity type I IgE Fc receptor (FceRI alpha, and prevent mast cell degranulation. Herein we propose the study that protective IgE B cell epitopes may be constrained in the loops of scaffold of green fluorescent protein (GFP). GFP contains 11 beta-pleated sheets which constrain loops of distinct regions. Loops corresponding to the IgE binding to FceRI alpha will be cloned and expressed. Antibodies raised to the constrained antigenized B cell epitopes will block human IgE binding to recombinant human FceRI alpha receptor in a high throughput assay (Aim I).Herein, we propose to determine the nature of anti-IgE and whether induction of anti-human IgE will ameliorate the IgE-mediated allergic diseases in mice. Thus, we will construct transgenic mice with B cells expressing membrane bound human IgE specific for nitrophenol (NP) as well as type I high affinity IgE Fc receptor alpha chain (FceRI alpha. We will determine whether active immunization will lead to protective anti-lgE which then removes NP specific IgE from the sera. Further, we will determine the degree of airway inflammation of these mice (Aim II)

Thesaurus Terms:
B lymphocyte, antiallergic agent, hypersensitivity, immunoglobulin E, vaccine development
active immunization, gene expression, green fluorescent protein, immunologic substance development /preparation
laboratory mouse, molecular cloning, transgenic animal

Institution:	IGE THERAPEUTICS, INC.
	6827 NANCY RIDGE DR
	SAN DIEGO, CA 92121
Fiscal Year:	2003
Department:
Project Start:	01-JAN-2003
Project End:	31-DEC-2004
ICD:	NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG:	ZRG1

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