Thursday, December 26, 2024 12/26/2024

Leveraging an ongoing longitudinal study of influenza vaccination to define immune signatures of response and risk of infection in older adults >75

Award Number: U01AI165826
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project summary Seasonal influenza (“flu”) remains a serious public health threat with the highest burden of severe disease and complications affecting older adults, particularly those over age 75. In addition to vaccine itself, responses to vaccination and vaccine effectiveness in older adults are likely influenced by comorbidity (e.g., frailty), immune senescent remodeling (i.e., immunosenescence and inflammaging), repeated annual vaccination, intra-seasonal immune waning, and virus strain variations both in vaccine formula and in circulation. Since 2014, we have established a study cohort in community-dwelling older adults >75. The cohort has accumulated 815 person-seasons with comprehensive demographic, clinical, functional and laboratory data, as well as banked pre- and post-vaccination serum, plasma, and peripheral blood mononuclear cell (PBMC) samples. We also identified 15 breakthrough flu infection cases with banked post-infection serum, plasma and PBMC samples. Importantly, 20 subjects participated in all 7 seasons, 36 in 6 seasons, 31 in 5 seasons, 16 in 4 seasons, and 165 in 3 seasons or less. Here, we propose to leverage this unique cohort and employ cutting edge immunologic research tools to develop state-of-the-art “immune signatures” reflecting both general immune status (distribution and function of immune cell subsets through high-dimensional flow analysis and RNA-Seq; cytokine profiling) and influenza-specific immunity (breadth and depth of flu-specific T cell repertoire; distribution/function of homotypic/heterotypic anti-flu T cells through flow analysis and scRNA-Seq; deep serological profiling of strain-specific and cross-reactive flu antibodies). Our objective is to characterize immune signatures and their intra- and inter-seasonal changes over time as determinants of vaccine responses and risk of breakthrough infection in older adults >75. Our specific aims are: 1) Characterize seasonal baseline (pre-existing) immune signatures as determinants of vaccine response and how they change over time. We will not only determine inter-season longitudinal trajectory, but also identify specific baseline immune signatures predict responses to vaccination; 2) Characterize seasonal immune signature responses to vaccination as determinants of risk of breakthrough infection and how they change over time. We will evaluate and compare differences and similarities of immune signature responses elicited by vaccination vs natural infection to explore immune mechanisms of vulnerability; and 3) Characterize intra-seasonal waning of immune signature responses to vaccination and its change across seasons through monthly blood sampling until the end of each flu season across multiple seasons. Upon completion, the proposed studies will advance our understanding of immune signatures as key immunologic mechanisms for vaccine responses and risk of breakthrough infection in a typical geriatric population. Ultimately, these studies will help define correlates of protection and develop more effective immunization strategies including a universal vaccine for this highly vulnerable subset of older adults.


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 = $1,583,019 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	4	11/25/2024	NON-COMPETING CONTINUATION	$1,583,019
														Subtotal = $1,583,019

Issue Date FY: 2024 ( Subtotal = $1,700,968 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	3	4/15/2024	NON-COMPETING CONTINUATION	$170,097
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	002	3	9/11/2024	NON-COMPETING CONTINUATION	$0
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	3	11/20/2023	NON-COMPETING CONTINUATION	$1,530,871
														Subtotal = $1,700,968

Issue Date FY: 2023 ( Subtotal = $1,688,993 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	2	11/17/2022	NON-COMPETING CONTINUATION	$1,688,993
2023	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	11/16/2022	NEW	$0
														Subtotal = $1,688,993

Issue Date FY: 2022 ( Subtotal = $1,632,946 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	12/9/2021	NEW	$1,632,946
														Subtotal = $1,632,946

Grand Total All Awards = $6,605,926

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Leveraging an ongoing longitudinal study of influenza vaccination to define immune signatures of response and risk of infection in older adults >75

Award Number: U01AI165826

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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