# Impact of preexisting immune profile in elderly on influenza vaccine response

> **NIH VA I01** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2024 · —

## Abstract

The decline in immunity with age results in poor responses to vaccines and novel pathogens. Pneumonia and
influenza are the most common causes of infectious hospitalization and death in people who are > 65 years of
age and yet the effectiveness of influenza vaccine lessens with age. An effective immune response requires the
appropriate interaction between the innate and the adaptive arms of the immune system and the proper balance
of activation and regulation. Aging affects multiple components of the immune system and we propose that the
cumulative defects and imbalances in the aging immune system that exist before vaccination contribute to
vaccine outcomes. This application will examine immune phenotypes in elderly and young participants before
annual influenza vaccination and determine how these phenotypes affect the B cell and T cell responses to
seasonal influenza vaccine. Aim 1 will determine whether older age, lower naïve T cell number or dysfunctional
naïve T cells prior to vaccination is associated with development of host T and B cell response to seasonal
influenza vaccine. We will evaluate age and naïve T cell phenotype in PBMC samples before vaccination to
determine whether these parameters correlate with host influenza specific T cell responses by ELISPOT (IFNγ
and IL2) and antibody responses by ELISA and hemagglutination inhibition assay (HAI). We will pay special
attention to a novel subset of T cells that are expanded in elderly, memory T cells with a naïve phenotype (Tmnp).
These cells express the lymph node homing receptor CCR7 but are transcriptionally and functional distinct from
naïve cells. In Aim 1a we will determine the antigen specificity of Tmnp cells in elderly by examining their specificity
to common viral antigens from influenza, CMV, and EBV using tetramers. In Aim 2, we will examine the
contribution of preexisting monocyte/macrophage phenotypes in elderly to influenza vaccine responses. We will
examine the phenotype of peripheral monocytes in elderly patients directly ex vivo using flow cytometry and
determine if the phenotype before vaccination is associated with the T and B cell response to influenza vaccine.
We will examine the systemic environment by measuring plasma levels of both inflammatory and anti-
inflammatory cytokines. Aim 2a will examine the influence of the elderly systemic microenvironment on monocyte
derived macrophage differentiation. We will generate monocyte-derived macrophages (MDM) in the presence of
autologous serum and then analyze the development of inflammatory (M1) or alternatively activated (M2)
macrophages and compare elderly and young MDM. In Aim 3 we will determine if T regulatory (Treg) or
dysfunctional T regulatory (TregDys) cell frequencies prevaccination are associated with impaired response to
influenza vaccine in the elderly. Although previous studies suggest there are elevated plasma levels of TGFβ
and an accumulation of Tregs with age, this contradicts the well-established obser...

## Key facts

- **NIH application ID:** 10721342
- **Project number:** 5I01BX006011-02
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Carey Lynn Shive
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10721342

## Citation

> US National Institutes of Health, RePORTER application 10721342, Impact of preexisting immune profile in elderly on influenza vaccine response (5I01BX006011-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10721342. Licensed CC0.

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