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CD4 T cell, germinal center, and antibody response defects in recurrent tonsillitis

Award Number: R01AI135193
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: 06/14/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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CD4 T cell, germinal center, and antibody response defects in recurrent tonsillitis - Project Summary It has remained a longstanding mystery why some children are susceptible to recurrent tonsillitis. Tonsillectomies are the most common pediatric surgery in America, with recurrent tonsillitis associated with S. pyogenes (group A streptococcus, GAS) being a primary cause. We have preliminary data that there is an immunological basis for recurrent streptococcal tonsillitis. Antibody responses are a central part of the immune system. T follicular helper CD4 T cells (Tfh cells) are required for germinal centers, and thus the majority of high affinity antibody responses. Tfh cells have important roles in protection from infectious diseases. Much remains to be learned about Tfh cells. We have developed a novel method for quantifying pathogen-specific Tfh cells, the activation immune marker (AIM) assay. The goal of this proposal is to ascertain the immunologic mechanisms tied to recurrent strep throat, and the GAS virulence factors that cause recurrent tonsillitis disease. Completion of this study could help identify children who are likely to be susceptible to recurrent strep throat, and mechanistic studies proposed herein could allow for rational design of countermeasures to prevent the disease in the future. During the course of the studies on tonsillitis in children exposed to SARS-CoV-2 antigens either naturally or through vaccination, differences in SARS-CoV-2-specific antibody responses and relative frequencies of memory versus germinal center B cells were noted. Preliminary data suggested that these differences may be, at least in part, be related to differences in the age of the child and prior history of responses to common cold coronaviruses. These observations provide a unique opportunity to compare responses to GAS and SARS-CoV-2 within the same pediatric cohort and to determine common vs. pathogen-specific variations in pediatric germinal center responses.


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: 2025 ( Subtotal = $0 )
2025	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	9/25/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	6/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $450,000 )
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	5	6/9/2022	SUPPLEMENT FOR EXPANSION	$112,500
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	6/2/2022	NON-COMPETING CONTINUATION	$337,500
														Subtotal = $450,000

Issue Date FY: 2021 ( Subtotal = $450,000 )
2021	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	5/25/2021	NON-COMPETING CONTINUATION	$450,000
														Subtotal = $450,000

Issue Date FY: 2020 ( Subtotal = $450,000 )
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	5/8/2020	NON-COMPETING CONTINUATION	$450,000
														Subtotal = $450,000

Issue Date FY: 2019 ( Subtotal = $450,000 )
2019	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	5/21/2019	NON-COMPETING CONTINUATION	$450,000
														Subtotal = $450,000

Issue Date FY: 2018 ( Subtotal = $450,000 )
2018	2018	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	6/14/2018	NEW	$450,000
														Subtotal = $450,000

Grand Total All Awards = $2,250,000

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CD4 T cell, germinal center, and antibody response defects in recurrent tonsillitis

Award Number: R01AI135193

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: 06/14/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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