Recent studies indicate that food allergy is the leading cause of anaphylaxis treated in American hospital emergency departments, and it is estimated that about 100 deaths occur each year in the US due to food-induced anaphylaxis. Peanut allergy accounts for the majority of these severe anaphylactic reactions. Given the lifelong nature of peanut allergy, these findings highlight the need for novel and effective therapeutic strategies. DNA-based immunization has been an attractive approach in altering the host immune response to antigen (Ag). Recently, the efficacy of intramuscular DNA-based immunization approach in the suppression of IgE synthesis and Th2- associated immune responses has been suggested. The proposed study is directly aimed at determining the immunologic basis of gene immunization, and exploring the utility of this approach in modulating peanut allergen-induced hypersensitivity. The model for this study is hypersensitivity to peanut allergens in an inbred strain of mice (C3H), in which several quantitative parameters of hypersensitivity, including symptom score, the levels of serum specific IgE, plasma histamine, and mast cell degranulation are established. Ara h 2 (17kD) is a major allergen in peanuts, and the T- cell response to Ara h2 appears to be dominant and common in both humans and sensitized C3 mice. In this application, the investigators propose to: (i) generate Ara h2-gene expression constructs, (ii) identify critical Ag-presenting cells; (iii) determine the effects of DNA immunization on peanut allergen-induced IgE synthesis and hypersensitivity, and (iv) examine the modulatory mechanism of DNA-based immunization in peanut hypersensitivity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI043668-01
Application #
2694406
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Nowak-Wegrzyn, Anna; Sampson, Hugh A (2006) Adverse reactions to foods. Med Clin North Am 90:97-127
Sicherer, Scott H; Munoz-Furlong, Anne; Sampson, Hugh A (2004) Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol 114:159-65
Li, Xiu-Min; Sampson, Hugh A (2004) Novel approaches to immunotherapy for food allergy. Clin Allergy Immunol 18:663-79
Shreffler, Wayne G; Beyer, Kirsten; Chu, Te-Hua Tearina et al. (2004) Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol 113:776-82
Nowak-Wegrzyn, Anna; Sampson, Hugh A (2004) Food allergy therapy. Immunol Allergy Clin North Am 24:705-25, viii
Li, Xiu-Min; Srivastava, Kamal; Grishin, Alexander et al. (2003) Persistent protective effect of heat-killed Escherichia coli producing ""engineered,"" recombinant peanut proteins in a murine model of peanut allergy. J Allergy Clin Immunol 112:159-67
Sicherer, Scott H; Munoz-Furlong, Anne; Sampson, Hugh A (2003) Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol 112:1203-7
Li, Xiu-Min; Srivastava, Kamal; Huleatt, James W et al. (2003) Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model. J Immunol 170:3289-95
Li, X M; Zhang, T F; Huang, C K et al. (2001) Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model. J Allergy Clin Immunol 108:639-46
Lee, S Y; Huang, C K; Zhang, T F et al. (2001) Oral administration of IL-12 suppresses anaphylactic reactions in a murine model of peanut hypersensitivity. Clin Immunol 101:220-8

Showing the most recent 10 out of 16 publications