Wednesday, October 9, 2024 10/9/2024

IgE antibodies to the mammalian oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal): immunology, epidemiology and relevance to allergic and inflammatory disease

Award Number: R37AI020565
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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SUMMARY Alzheimer’s disease (AD) is a leading cause of death among older adults. Its high prevalence, amounting to one third of all seniors, warrants new research directions on the pathogenesis of AD that can unlock new treatments. Studying AD in the context of emerging allergic diseases presents a key opportunity in this regard. Emerging allergic diseases to food allergens present an important public health problem whose ramifications may extend beyond the gastrointestinal tract to other organ systems, including the brain. This project capitalizes on pioneering work by the study team on “alpha-gal syndrome” (AGS), by exploring how neuroinflammatory profiles relate to tick-induced allergy to mammalian meat in patients sensitized to the carbohydrate allergen, galactose- alpha-1,3-galactose (alpha-gal). The proposed work builds on the idea that tick bites promote systemic inflammatory processes that could adversely impact the brain. This notion is bolstered by recent data, including that of the study team, to support a link between sensitization to alpha-gal and cardiovascular disease. The central hypothesis is that patients with IgE to alpha-gal develop inflammatory profiles that promote neuroinflammation. Given that AGS is an antigen-driven disorder, we further posit that T cells are pivotal to this process. The project leverages an extensive set of existing specimens and data from highly characterized cohorts spanning the spectrum of sensitization to alpha-gal, as well as a unique comparison group of chronically inflamed patients suffering from post-acute sequelae of severe COVID-19 illness. The approach in Aim 1A will define neuroinflammatory states using an unsupervised integrative approach across hundreds of serum samples from patients with alpha-gal sensitivity. This will include assaying canonical and candidate biomarkers of AD using ultrasensitive assays, in conjunction with a broad set of cytokines and chemokines, and then defining discrete inflammatory states using cluster analyses. Longitudinal assessments will be performed in a subsample of 100 patients with IgE to alpha-gal who return for a follow up visit at 3-10 years after their initial visit, in order to monitor the development of neuroinflammatory profiles in relation to change in IgE and decline in neurocognitive function. Profiles will be validated using samples from patients with AD and in COVID-19 patients with neurocognitive sequelae. In Aim 1B, deep T-cell profiling using spectral flow cytometry and machine learning methods will be used to elucidate complex T-cell signatures that constitute “functional networks” governing neuroinflammatory states that are defined in Aim 1A. Establishing a new paradigm for the immunopathogenesis of AD will identify novel avenues for exploring the interaction between AD and allergic disease, and ultimately aid in the design of new therapies for this devastating disease.


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: 2024 ( Subtotal = $1,245,603 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	002	40	8/21/2024	SUPPLEMENT FOR EXPANSION	$262,801
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	40	5/29/2024	NON-COMPETING CONTINUATION	$622,802
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	40	6/24/2024	SUPPLEMENT FOR EXPANSION	$360,000
														Subtotal = $1,245,603

Issue Date FY: 2023 ( Subtotal = $622,802 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	39	3/6/2023	EXTENSION WITH OR WITHOUT FUNDS	$622,802
														Subtotal = $622,802

Issue Date FY: 2022 ( Subtotal = $986,177 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	38	8/5/2022	NON-COMPETING CONTINUATION	$363,375
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	38	6/1/2022	NON-COMPETING CONTINUATION	$622,802
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	002	38	9/22/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $986,177

Issue Date FY: 2021 ( Subtotal = $622,802 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	37	6/9/2021	NON-COMPETING CONTINUATION	$622,802
														Subtotal = $622,802

Issue Date FY: 2020 ( Subtotal = $752,002 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	35	3/9/2020	SUPPLEMENT FOR EXPANSION	$129,200
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	36	6/12/2020	NON-COMPETING CONTINUATION	$622,802
														Subtotal = $752,002

Issue Date FY: 2019 ( Subtotal = $459,892 )
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	35	6/13/2019	NON-COMPETING CONTINUATION	$445,840
2019	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	34	2/11/2019	COMPETING CONTINUATION	$14,052
														Subtotal = $459,892

Issue Date FY: 2018 ( Subtotal = $588,085 )
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	34	7/25/2018	COMPETING CONTINUATION	$129,200
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	34	6/15/2018	COMPETING CONTINUATION	$458,885
														Subtotal = $588,085

Issue Date FY: 2001 ( Subtotal = $403,972 )
2001	2001	UNIVERSITY OF VIRGINIA	PO BOX 9003	CHARLOTTESVILLE	VA	22906	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	18	6/7/2001	NON-COMPETING CONTINUATION	$403,972
														Subtotal = $403,972

Issue Date FY: 2000 ( Subtotal = $394,371 )
2000	2000	UNIVERSITY OF VIRGINIA	PO BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	17	4/27/2000	NON-COMPETING CONTINUATION	$394,371
														Subtotal = $394,371

Issue Date FY: 1999 ( Subtotal = $385,053 )
1999	1999	UNIVERSITY OF VIRGINIA	PO BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	16	5/6/1999	NON-COMPETING CONTINUATION	$385,053
														Subtotal = $385,053

Issue Date FY: 1998 ( Subtotal = $501,004 )
1998	1998	UNIVERSITY OF VIRGINIA	PO BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	15	5/26/1998	NON-COMPETING CONTINUATION	$501,004
														Subtotal = $501,004

Grand Total All Awards = $6,961,763

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IgE antibodies to the mammalian oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal): immunology, epidemiology and relevance to allergic and inflammatory disease

Award Number: R37AI020565

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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