Grantee Research Project Results

Final Report: Safety Assessment of Dietary Proteins for Allergenicity Using an Adjuvant-Free Mouse Model

EPA Grant Number: R833133
Title: Safety Assessment of Dietary Proteins for Allergenicity Using an Adjuvant-Free Mouse Model
Investigators: Gangur, Venugopal , Tempelman, Robert J.
Institution: Michigan State University
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2006 through September 30, 2009 (Extended to March 31, 2010)
Project Amount: $447,774
RFA: Biotechnology: Potential Allergenicity of Genetically Engineered Foods (2006) RFA Text | Recipients Lists
Research Category: Human Health

Objective:

Food allergy is a serious public health problem of international significance that is growing world-wide. Specific reasons for this increase in food allergy are not completely understood at present. Whether genetically engineered (GE) foods contribute to this problem is largely unknown. Assessment of the allergenic potential of GE foods is a major challenge facing the regulatory agencies and the agro-biotech industry. Although expert panels suggest the use of animal models as one of the methods for assessment of allergenic potential of GE foods, validated animal models are not available at present.

The goal of this project was to test the validity of a novel adjuvant-free transdermal sensitization/oral disease elicitation (TS/OE) model of food allergy that we had previously reported (Birmingham et al Int Arch Allergy Immunol 2007;144(3): 203-10; Navuluri et al 2006 Int Arch Allergy Immunol 2006;140:270-276). Here, we tested the hypothesis that this mouse model will be highly reliable in discerning food proteins that have or do not have intrinsic allergenic sensitization potential in humans.

The two specific objectives for this project were to determine: (1) the positive predictive value (i.e., sensitivity) of the mouse-model; and (2) the negative predictive value (i.e., specificity) of the mouse model for testing allergenicity of dietary proteins.

Summary/Accomplishments (Outputs/Outcomes):

The data obtained during this project demonstrate that: (1) the allergenicity readouts in this mouse model are dependent on the number of exposures to the allergenic protein; (2) seven human allergenic proteins (hazelnut, cashew nut, sesame seed, milk, shellfish, egg, fish) produce all three readouts of allergenicity in this mouse model; (3) six human non-allergenic proteins (kidney bean, Pinto bean, blue berry, sorghum, pigeon pea, mung bean) were non-allergenic in this model based on clinical scores and hypothermia readouts; and (4) Amaranth seed protein that has no history of human allergenicity and therefore presumed to be non-allergenic, tested positive for all three readouts of allergenicity.

Conclusions:

These data suggest that the TS/OE mouse model has very promising positive and negative predictive value for assessment of food protein allergenicity. These data also warrant further validation of this mouse model towards the long-term goal of using it for predicting allergenic potential novel food proteins. In particular, it is critical to determine: (1) whether the threshold doses in this model are similar to humans, and (2) whether this model has the potential to distinguish purified isolated allergenic vs. non-allergenic proteins.

Journal Articles on this Report : 8 Displayed | Download in RIS Format

Publications Views
Other project views:	All 23 publications	8 publications in selected types	All 8 journal articles

Publications
Type	Citation	Project	Document Sources
Journal Article	Gonipeta B, Parvataneni S, Tempelman RJ, Gangur V. An adjuvant-free mouse model to evaluate the allergenicity of milk whey protein. Journal of Dairy Science 2009;92(10):4738-4744.	R833133 (2009) R833133 (Final)	Full-text: Journal of Dairy Science-HTML Exit Abstract: Journal of Dairy Science-Abstract Exit Other: Journal of Dairy Science-PDF Exit
Journal Article	Gonipeta B, Parvataneni S, Paruchuri P, Gangur V. Long-term characteristics of hazelnut allergy in an adjuvant-free mouse model. International Archives of Allergy and Immunology 2010;152(3):219-225.	R833133 (2009) R833133 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: Karger-Abstract Exit
Journal Article	Gonipeta B, Duriancik D, Kim E, Gardner E, Gangur V. Identification of T-and B-cell subsets that expand in the central and peripheral lymphoid organs during the establishment of nut allergy in an adjuvant-free mouse model. ISRN Allergy 2013;509427.	R833133 (Final) R834822 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Hindawi - Full Text HTML & PDF Exit
Journal Article	Gonipeta B, Kim E, Gangur V. Mouse models of food allergy: how well do they simulate the human disorder? Critical Reviews in Food Science and Nutrition 2015;55(3):437-452.	R833133 (Final) R834822 (Final)	Abstract from PubMed Abstract: Taylor&Francis - Abstract Exit
Journal Article	Kelly C, Gangur V. Sex-disparity in food allergy: evidence from the PubMed database. Journal of Allergy 2009;2009:159845.	R833133 (2009) R833133 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Hindawi-Full Text HTML Exit Abstract: Hindawi Publishing Corporation Exit
Journal Article	Parvataneni S, Gonipeta B, Tempelman RJ, Gangur V. Development of an adjuvant-free cashew nut allergy mouse model. International Archives of Allergy and Immunology 2009;149(4):299-304.	R833133 (2008) R833133 (Final)	Abstract from PubMed Abstract: Karger-Abstract Exit
Journal Article	Parvataneni S, Birmingham NP, Gonipeta B, Gangur V. Dominant, non-MHC genetic control of food allergy in an adjuvant-free mouse model. International Journal of Immunogenetics 2009;36(5):261-267.	R833133 (2009) R833133 (Final)	Abstract from PubMed Abstract: Wiley Online-Abstract Exit
Journal Article	Parvataneni S, Gonipeta B, Acharya HG, Gangur V. An Adjuvant-Free Mouse Model of Transdermal Sensitization and Oral Elicitation of Anaphylaxis to Shellfish. International Archives of Allergy and Immunology 2015;168(4):269-276.	R833133 (Final) R834822 (Final)	Abstract from PubMed Full-text: Karger-Full Text PDF Exit Abstract: Karger-Abstract & Full Text HTML Exit

Supplemental Keywords:

Food allergy, food safety, allergen, systemic anaphylaxis, exposure, hazard assessment, mouse model, potency testing, dose-response, genetic engineering, allergenicity, Health, Scientific Discipline, Health Risk Assessment, Risk Assessments, Allergens/Asthma, Biochemistry, dietary protein, food allergenicity, genetically engineered food, oral allergy syndrome, bioinformatics, allergic response

Progress and Final Reports:

Original Abstract

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.