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Regulation Of Lung Immunity By Antibody Glycosylation

Award Number: R01AI178298
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/13/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Regulation Of Lung Immunity By Antibody Glycosylation - The glycans present on IgG antibodies are key determinants of immune complex (IC) signaling by FcγRs, with modulations in IgG glycosylation triggering distinct antibody effector functions in response to infection or immunization. While FcγR signaling pathways are broadly characterized, with established functions in cell maturation, phagocytosis, production or release of soluble factors, and suppression or modulation of activating signals, little is known about how these responses are integrated at the tissue level. Of particular interest is understanding how IgG glycoforms regulate antibody-mediated functions in the lung, the immune interface for respiratory pathogens and a tissue with unique cellular features, including lung-specific, FcγR-expressing cells. Using a newly developed system in mice that express human FcγRs, we have found that IC glycosylation, specifically fucosylation and sialylation, can regulate lung inflammatory responses. We now propose to examine the role of distinct IgG IC glycoforms in regulating the outcomes of SARS-CoV-2 and IAV virus infections, as we have observed that different patterns of IC glycosylation correlate with disease risk in these two infections. We will study how signaling by differentially glycoslylated IC impacts viral and host immune readouts in SARS-CoV- 2 and IAV virus infections, and we will define molecular mechanisms governing the regulation of lung inflammation by IC. Our hope is that these studies will reveal aspects of how the host IgG glycome contributes to heterogeneous outcomes of infection with SARS-CoV-2 and IAV viruses and reveal mechanisms that can be targeted to prevent the severe lung inflammation that leads to ARDS and mortality in these and potentially other respiratory infections.


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 = $918,433 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	3	1/5/2026	NON-COMPETING CONTINUATION	$918,433
														Subtotal = $918,433

Issue Date FY: 2025 ( Subtotal = $860,851 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	2	12/5/2024	NON-COMPETING CONTINUATION	$860,851
														Subtotal = $860,851

Issue Date FY: 2024 ( Subtotal = $901,076 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	1	2/13/2024	NEW	$812,331
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	1	9/3/2024	NEW	$88,745
														Subtotal = $901,076

Grand Total All Awards = $2,680,360

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Regulation Of Lung Immunity By Antibody Glycosylation

Award Number: R01AI178298

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/13/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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