# Project 3: Effects of Age on Cellular, Transcriptomic and Biochemical Influenza Signatures

> **NIH NIH U19** · YALE UNIVERSITY · 2021 · $385,332

## Abstract

Influenza remains a worldwide public health threat in the 21st Century. Its impact is magnified by a vaccine that
affords incomplete protection whose composition usually changes annually, and by the episodic appearance of
new pandemic strains, such as the A/California H1N1 strain that emerged in 2009. Influenza has a particularly
acute impact in in the geriatric age group, with 90% of the 20,000-40,000 annual deaths in the United States
attributed to influenza occurring in individuals over the age of 65. This proposal, like all of the Projects in this
Human Immunology Project Consortium application, seeks to identify the host factors associated with immune
response in humans. Here we focus on factors contributing to influenza vaccine response, and how these
factors and pathways are affected by age and functional status. In this proposal, we will leverage our expertise
in carrying out studies in human immunology, particularly our studies that have identified innate immune and
gene expression signatures of vaccine response to standard-dose vaccine and how aging affects these
signatures. In particular, we found an unexpected mitochondrial biogenesis signature that was strongly
associated with vaccine antibody response, and this finding, together with preliminary metabolomic data, has
led us to propose employing already-collected serum samples to derive biochemical signatures of vaccine
response that will be integrated with the gene expression, cellular and immunologic signatures already
elucidated for young and older adults in this cohort. We also propose to elucidate new insights into the biologic
basis of frailty, a geriatric syndrome characterized by decreased physiologic reserve and stress resistance that
is associated with increased mortality and disability. We will also gain new insights into the high-dose
influenza vaccine recently approved for older adults, administering this vaccine to a cohort of young (age 21-
30), non-frail older and frail older (≥ 70) adults. For these studies, we will leverage large databases of older
adults established by the Yale Program on Aging and the expertise and track record of experts in frailty and
disability at Yale such as Dr. Thomas Gill. Samples obtained prior to and following vaccination will undergo
detailed analyses by CyTOF (Core C) for innate and adaptive immune cell composition (including novel studies
of the platelet lineage), activation, and cytokine production. We will also carry out unbiased studies of innate
immune pattern recognition receptor function. These findings will be integrated with single-cell RNA-seq
studies utilizing the nanowell platform in Core C to isolate individual cells from lineages identified to change in
the context of vaccination, and with metabolic analyses of serum and cells pre- and post-vaccine. Such
metabolomic analyses will identify pathways reflecting the integration of numerous genetic signaling inputs,
and will provide additional insights into human influenza vacc...

## Key facts

- **NIH application ID:** 10079825
- **Project number:** 5U19AI089992-10
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Albert C Shaw
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,332
- **Award type:** 5
- **Project period:** 2010-07-12 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079825

## Citation

> US National Institutes of Health, RePORTER application 10079825, Project 3: Effects of Age on Cellular, Transcriptomic and Biochemical Influenza Signatures (5U19AI089992-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10079825. Licensed CC0.

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