# The Impact of Aging and HIV Infection on Immunologic and Transcriptomic Signatures of Influenza Vaccine Response

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $779,116

## Abstract

It is estimated that approximately half of HIV-infected individuals in the United States are over 50 years of age.
Aging of the HIV-infected population has linked alterations in immune responses associated with age and the
immunologic consequences of chronic HIV infection. This intersection of HIV and aging will influence host
defense against infection and response to vaccines. As a result, understanding the nexus of HIV-associated
immune activation and immunosenescence takes on particular urgency. We will leverage insights from our
published and ongoing studies on the effects of aging on dysregulated innate immune pattern recognition
receptor (PRR) function, a novel population of pro-inflammatory IL-7 receptor alow effector memory (EM) CD8 T
cells that are expanded in HIV-negative older adults, and on expansion of EM CD8 T cells in older HIV-positive
adults. We have also elucidated gene expression and immunologic signatures of influenza vaccine response
in young and older HIV-negative adults. These findings position us to illuminate the effects of aging and HIV
infection on innate and adaptive immune function, particularly following influenza vaccination. To address
these questions, we have assembled an interdisciplinary group of investigators with expertise in the study of
aging of the innate and adaptive human immune systems, and in HIV immunology, biology and clinical care.
Our overarching hypothesis is that the pro-inflammatory environment associated with age and with suppressed
HIV infection potentiates immunosenescence in older adults with HIV disease. To test this hypothesis, we will
enroll young (age 21-35) and older (age over 65) adults with HIV infection receiving high-dose influenza
vaccine. We will employ state of the art methods including multichannel mass cytometry on whole blood to
assess development and activation of major populations (e.g. monocytes, dendritic cells, NK cells,
lymphocytes, neutrophils), including novel studies of platelets pre- and post-vaccine. We will evaluate innate
immune PRR function (including Toll-like and NOD-like receptor family members), where we previously found
age-associated alterations in cytokine production and costimulatory protein expression that were related to
influenza vaccine response. We will also study T cell responses to in vitro vaccine antigen stimulation,
including the IL-7 receptor alow EM CD8 T cell subset. Statistical modeling will include clinical and functional
covariates (e.g. CD4+ T cell count, estimated duration of HIV disease and of ART, medical co-morbidities,
medication use, functional status). Finally, we will derive gene expression signatures of influenza vaccine
response in young and older adults with HIV disease, and compare these to those we previously identified in
HIV-negative adults. We will employ state of the art analytic methods to integrate gene expression and
immunologic data to obtain a comprehensive view of the human immune response in the context of age and
i...

## Key facts

- **NIH application ID:** 10183118
- **Project number:** 5R01AG055362-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Insoo Kang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $779,116
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183118

## Citation

> US National Institutes of Health, RePORTER application 10183118, The Impact of Aging and HIV Infection on Immunologic and Transcriptomic Signatures of Influenza Vaccine Response (5R01AG055362-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10183118. Licensed CC0.

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