Immunologic Trajectories of Peanut Desensitization (INROADS)
openNIAID - National Institute of Allergy and Infectious Diseases
SUMMARY – Overall Application: Immunologic Trajectories of Peanut Desensitization (INROADS)
Peanut allergy has tripled in prevalence in recent decades, affecting nearly 2% of adults and up to 5% of
children in some US regions. Peanut allergy is typically lifelong, can be fatal, and impacts quality of life. Our
group and others performed the studies resulting in the recent FDA approvals of a commercial peanut oral
immunotherapy (OIT) and an anti-IgE monoclonal antibody, omalizumab. These therapies can raise the
reaction threshold and provide safety from accidental exposures for approximately 67% of patients.
Additionally, in a prior period of our AADCRC grant, we focused on children whose reaction threshold to
peanut was higher than the children included in the registration trials of the expensive pharmaceutical
products. We demonstrated that nearly half of the peanut allergic population could be treated safely and
effectively with inexpensive, retail store-purchased, home-measured peanut. These findings are revolutionizing
desensitization therapy for peanut allergy and provide options for our patients other than strict peanut
avoidance. However, in clinical practice, there is no way to predict response to therapy, and there is an
insufficient understanding of the mechanisms that are involved in the success, or lack thereof, from these
therapies. This proposal, Immunologic Trajectories of Peanut Desensitization (INROADS), builds upon
discoveries and techniques from our prior AADCRC and our additional studies to address the knowledge gaps
of these desensitization therapies that will improve personalized care and provide mechanistic insights for
better treatments. INROADS will address the overarching hypothesis that dynamic changes in
circulating cellular subpopulations and molecular networks are mechanistically linked to peanut
desensitization outcomes. Project 1, MICRO-TRACK, will use high-dimensional immune profiling, allergen-
specific T cell assays, and in vitro stimulation models to identify predictive biomarkers and mechanisms of
immunologic control of desensitization therapies. Project 2, SPADE, will complement this effort using
transcriptomics and machine learning to identify signatures of desensitization and desensitization classifiers to
provide mechanistic insights and clinical tools for treating individuals with peanut allergy. We will synergize
Mount Sinai’s cutting-edge clinical therapeutics program via a Clinical Core (PATHWAYS) to provide clinical
data and biosamples from oral food challenge tests performed before and following desensitization treatments.
The two research projects, interactions with the Clinical Core, management of biosamples and data, and
communications with NIAID and the AADCRC network will be coordinated and supported by an Administrative
Core and a Data Stewardship Core. In addition to creating a rich resource of clinical, immune, and molecular
data that will be made publicly available for the research community, our integrated program will advance
personalized medicine, enrich mechanistic understandings, and potentially identify new therapeutic targets for
peanut allergy that will be informative for allergy to any food.
Up to $1.4M
health research