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A deep longitudinal analysis of next generation influenza vaccines in older adults

Award Number: U01AI165452
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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A deep longitudinal analysis of next generation influenza vaccines in older adults - PROJECT SUMMARY The WHO estimates that annual epidemics of influenza result in 3-5 million cases of severe illness and 300,000- 500,000 deaths. 90% of influenza-related deaths occur in older adults despite widespread vaccination programs with vaccines tailored for this high-risk group. The estimated effectiveness of the influenza vaccine in the U.S. for the 2018-2019 influenza season overall was 47%, but only 12-13% in older adults. There is therefore an urgent need to understand the mechanisms that are turned on/off in older adults that result in their limited response rate to the most commonly used influenza vaccine, Fluzone® High-Dose. There is also a need to understand whether and why next-generation influenza vaccines might be more efficacious. Immunosenescence is known to be associated with declines in optimal B cell and T cell adaptive immunity, however, our overall understanding of the mechanisms of immunosenescence is incomplete. The central goal of this proposal is to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults through establishment of the 3FluAging cohort of healthy older adults who will be vaccinated with three different influenza vaccines three years in a row. We hypothesize that aging impacts specific regulatory mechanisms of humoral immunity to reduce vaccine effectiveness. In Aim 1, we will establish a cohort of 60 healthy older adults (≥65yrs) who will sequentially receive three different annual influenza vaccines, with serial blood and microbiome sample collection during three years of follow-up. Participants will undergo regular clinical assessments. In Aim 2, we will decipher the magnitude and immunodominance pattern of the humoral response to influenza virus in healthy older individuals upon vaccination. For each vaccine, we will characterize antibody titer and quality and will define responders and non-responders. In Aim 3, we will characterize the epigenome, transcriptome, cytokine production, and cell proportions of blood leukocytes in vaccinated healthy older participants. We will identify specific (epi)genomic and functional signatures, and their longevity, associated with vaccine response. We will also sequence all participants to uncover the role of genetic variation on influenza vaccine responses. In Aim 4, we will assess the function of T helper cells and antigen presenting cells, specifically dendritic cells, in influenza vaccine responders and non-responders. By identifying responders and non-responders for each vaccine and integrating these data with baseline immune status multi-omic signatures, we will determine which immune features can predict vaccine responsiveness. We expect to identify humoral immunity pathways that are altered in aging that can be used as the basis for designing novel approaches to boost efficacy of the most commonly used, as well as emerging, influenza vaccines.


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 = $919,804 )
2026	2026	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	000	5	12/30/2025	NON-COMPETING CONTINUATION	$919,804
														Subtotal = $919,804

Issue Date FY: 2025 ( Subtotal = $1,843,486 )
2025	2025	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	000	4	11/27/2024	NON-COMPETING CONTINUATION	$1,843,486
														Subtotal = $1,843,486

Issue Date FY: 2024 ( Subtotal = $2,465,186 )
2024	2024	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	000	3	12/15/2023	NON-COMPETING CONTINUATION	$2,218,669
2024	2024	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	001	3	4/19/2024	NON-COMPETING CONTINUATION	$246,517
														Subtotal = $2,465,186

Issue Date FY: 2023 ( Subtotal = $2,195,905 )
2023	2023	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	000	2	12/19/2022	NON-COMPETING CONTINUATION	$2,195,905
2023	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	001	1	12/20/2022	NEW	$0
														Subtotal = $2,195,905

Issue Date FY: 2022 ( Subtotal = $1,622,607 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Allergy and Infectious Diseases Research	000	1	12/27/2021	NEW	$1,622,607
														Subtotal = $1,622,607

Grand Total All Awards = $9,046,988

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A deep longitudinal analysis of next generation influenza vaccines in older adults

Award Number: U01AI165452

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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