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Defining oral and systemic immune modulation in peanut sublingual immunotherapy

Award Number: F31AI200255
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/24/2026
PERIOD OF PERFORMANCE END DATE: 12/23/2027

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Defining oral and systemic immune modulation in peanut sublingual immunotherapy - PROJECT SUMMARY/ABSTRACT Peanut allergies affect 2-3% of children in the US, are increasing in prevalence, and pose a risk of life-threatening reactions upon accidental ingestion. Together, these factors lead to decreased quality of life, and therefore, safe and effective treatments are needed. While the FDA has approved two therapies for peanut allergy, Palforzia (peanut oral immunotherapy) and omalizumab (anti-IgE biologic) each have limitations including side effects, administration restrictions, and cost. Peanut sublingual immunotherapy (SLIT) has shown promise in several studies, demonstrating similar efficacy and fewer side effects, as a recent cohort of peanut-allergic children resulted in nearly 80% achieving desensitization and 60% achieving remission, with mainly local transient side effects. Preliminary data we have generated has shown that peanut SLIT results in systemic immune modulation, apparent from decreases in peanut-specific IgE, increases in peanut-specific IgG4, and decreases in basophil activation. However, we have not yet evaluated the local immune responses modulated by peanut SLIT, and we do not understand why some individuals are successful on peanut SLIT, while others fail treatment. To address these gaps in knowledge, we will evaluate the longitudinal effect of peanut SLIT on the mucosal immune response using saliva samples from this peanut-allergic cohort and our mouse model of peanut SLIT. We hypothesize that peanut SLIT results in activation and trafficking of tolerogenic dendritic cells to draining lymph nodes, leading to the induction of Tregs and production of protective, peanut-specific IgA and IgG4. In Aim 1, we will determine the kinetics of the mucosal immune responses induced from peanut SLIT by measuring peanut- specific and peanut-component IgA and IgG4 from saliva collected from participants throughout treatment. We will also use the Olink platform to define the proteomic profiles from saliva samples and determine how salivary cytokines correlate with clinical remission. By comprehensively profiling the immune response induced by peanut SLIT, we will determine if any of these measures can be used as biomarkers to predict success or monitor progress on therapy. In Aim 2, we will determine the immunological mechanisms of peanut SLIT using our mouse model of peanut allergy. We will monitor the trafficking of peanut to the cervical lymph nodes and use single-cell RNA sequencing techniques to characterize the immune cells and gene expression profiles induced throughout peanut SLIT. We will also measure peanut-specific immunoglobulins in the saliva and serum from mice throughout the experiment to correlate with peanut challenge outcomes and immune cell populations. Together, these approaches in our mouse model will allow us to understand the mechanisms of immune modulation induced by peanut SLIT in ways that we cannot in humans. These studies will provide essential insights into the mucosal and systemic immunological mechanisms underlying peanut SLIT so that we can induce long-lasting efficacy in more peanut-allergic individuals.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $41,816 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Allergy and Infectious Diseases Research	000	1	6/30/2026	NEW	$41,816
														Subtotal = $41,816

Grand Total All Awards = $41,816

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Defining oral and systemic immune modulation in peanut sublingual immunotherapy

Award Number: F31AI200255

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/24/2026

PERIOD OF PERFORMANCE END DATE: 12/23/2027

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