# Metformin to improve immunological health and vaccine responses

> **NIH NIH K23** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $159,373

## Abstract

Abstract
This Mentored Patient-Oriented Research Career Development Award (K23) seeks to equip Dr. Grace Lee with
the skill requisites needed to develop into a leading translational geroscientist focused on evaluating
pharmacological interventions to improve immunological health. The career development program outlines
supervised research and educational activities to achieve the following training objectives: (1) gain skills in
integrating clinical and molecular approaches in prospective clinical trials of aging; (2) interpret and apply
immunogenetic data to characterize immune resilience in aging; and (3) gain skills needed to transition to
independent funding. Deterioration of immune function is a hallmark of most age-associated diseases. Thus,
identifying therapeutically modifiable pathways that underpin the aging-associated immune decline are needed
to improve health span/lifespan. The overall objective of this study is to test a widely used diabetes drug,
metformin, to improve immunological integrity as a marker of resilience. This K23 application builds on
preliminary data acquired while as a RL5 Pepper Center Scholar, which (i) identified that metformin was
associated with improved pneumococcal conjugate vaccine (PCV13) responses in mice, and (ii) established
feasibility of a clinical trial using metformin to improve immunological resilience in older adults. Additionally,
through evaluation of a ~70,000 person cohort, working with my mentor, we have identified genomic and
immunologic correlates of an immunosenescence-mediating program that contributes to age-associated
decline in immunological integrity, including vaccine responses and mortality. For this K23, we propose to
conduct a pilot double-blind randomized placebo-controlled clinical trial of adults 50 to 65 years of age. Eligible
subjects will be randomized in a 1:1 ratio to metformin (titrated to 2,000 mg/day) or placebo for a total duration
of 5 months. After completing a 16 week course of study drug, subjects will be administered the PCV13, then
followed for an additional 4 weeks on treatment. We will compare PCV13 vaccine responsiveness and
improvements in novel genomic signatures associated immunological integrity in adults treated with metformin
compared to placebo. The findings from this study will provide the necessary pilot data for future, more
definitive studies that will advance our understanding of metformin’s role on the aging immune system. This
proposal is supported by a mentorship team of renowned scientists in immunology/genomics (Dr. Ahuja), aging
research (Drs. Musi and Espinoza), and pneumococcal diseases (Dr. Restrepo), and an advisor in biostatistics
(Dr. Gelfond). This team, along with resources available through the San Antonio Pepper Center and Barshop
Institute for Longevity and Aging Studies, comprise an ideal environment for Dr. Lee to successfully reach her
goal to promote healthy aging.

## Key facts

- **NIH application ID:** 9953450
- **Project number:** 1K23AG066933-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Grace Choi Lee
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $159,373
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953450

## Citation

> US National Institutes of Health, RePORTER application 9953450, Metformin to improve immunological health and vaccine responses (1K23AG066933-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953450. Licensed CC0.

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