Peanut allergy (PA) is a severe form of food allergy for which Improved treatments are needed. However, few Studies have been conducted to optimize the safety of oral immunotherapy (OIT) for PA, to tailor OIT protocols according to the needs of individual PA patients, or to identify the immunological mechanism(s) underlying any long-lasting effects of oral immunotherapy (OIT) in such subjects. Specifically, It is not yet clear what factors will determine, in individual subjects, whether OIT induces tolerance (in which no set dally use of that food alleroen is needed to allow for its safe consumption). To address these challenges, the Stanford Alliance for Food Allergy Research (SAFAR) plans to link the findings of the Phase 2 clinical study proposed here in Project 1 with the results of each of the other 3 projects of the U19 proposal focused on mechanistic studies (Projects 2, 3 &4), as well as with the results ofthe immune metrics assays carried out by Scientific Core B. Each of these projects and Core B will use patient samples from Project 1 collected at screening and longitudinally throughout the clinical study to Integrate all data. We propose 3 main goals of our research for Project 1:
Specific Aim 1 : Test whether treatment of PA patients with OIT allows tolerance to be achieved (i.e., allows the subject to stop maintenance ingestion of peanut [during an """"""""avoidance period""""""""] for 3 months or more but then still undergo a successful double-blind placebo-controlled food challenge [DBPCFC] with peanut).
Specific Aim 2 : Determine whether treatment with our OIT protocol is safe in children and adults with peanut allergy (PA).
Specific Aim 3 : Evaluate to what degree current laboratory and clinical testing methods are associated with safety and tolerance outcomes (as identified in Specific Aims 1 and 2) in subjects with PA. By pursuing these aims, we will both: 1) provide the clinical samples, and the clinical outcome data, that will permit the innovative immune monitoring and mechanistic studies proposed in this U19 application to be accomplished, and 2) determine whether performing such immune monitoring has the potential to permit Individualization and optimization of safe and efficacious OIT protocols for individual PA patients.

Public Health Relevance

Food allergy is an important disease of children and adults that is in need of improved therapy. We propose a Study to test whether adult and pediatric patients with one of the most dangerous food allergies, peanut allergy, can become tolerant to peanuts after an oral immunotherapy regimen so that they may be able to eat peanut safely.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI104209-02
Application #
8605842
Study Section
Special Emphasis Panel (ZAI1-PA-I)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
$171,533
Indirect Cost
$62,277
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Ryan, John F; Hovde, Rachel; Glanville, Jacob et al. (2016) Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets. Proc Natl Acad Sci U S A 113:E1286-95
Levin, Mattias; King, Jasmine J; Glanville, Jacob et al. (2016) Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy. J Allergy Clin Immunol 137:1535-44
Yu, Wong; Freeland, Deborah M Hussey; Nadeau, Kari C (2016) Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 16:751-765
Hussey Freeland, Deborah M; Fan-Minogue, Hua; Spergel, Jonathan M et al. (2016) Advances in food allergy oral immunotherapy: toward tolerance. Curr Opin Immunol 42:119-123
Gaudenzio, Nicolas; Sibilano, Riccardo; Marichal, Thomas et al. (2016) Different activation signals induce distinct mast cell degranulation strategies. J Clin Invest 126:3981-3998
Chinthrajah, R Sharon; Hernandez, Joseph D; Boyd, Scott D et al. (2016) Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol 137:984-97
Galli, Stephen J (2016) The Mast Cell-IgE Paradox: From Homeostasis to Anaphylaxis. Am J Pathol 186:212-24
Mukai, Kaori; Gaudenzio, Nicolas; Gupta, Sheena et al. (2016) Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis. J Allergy Clin Immunol :
Pennington, Luke F; Tarchevskaya, Svetlana; Brigger, Daniel et al. (2016) Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange. Nat Commun 7:11610
Hoh, Ramona A; Joshi, Shilpa A; Liu, Yi et al. (2016) Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol 137:157-67

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