# Transcriptional and metabolic regulation of vaccine-elicited CD8+ T cell responses

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $460,469

## Abstract

PROJECT SUMMARY
Due to the overwhelming success of the new mRNA vaccines during the SARS-CoV2 pandemic, vaccines have
entered the public consciousness to a level not seen since the days of smallpox eradication and the polio
epidemic. It seems reasonable to assume that the established rules governing T cell responses to infections
might be useful in developing better subunit vaccine formulations. However, there is mounting evidence that the
immunological mechanisms relevant to adjuvant-elicited cellular immunity are vastly different than those
observed in response to infectious challenge. Over the last 20 years, we have published extensively on a growing
list of factors that highlight the mechanistic distinctions between vaccine-elicited (Tvacs) and infection-elicited
(Tinf) T cell responses in mice and non-human primates. Our most recent data has revealed additional features
mechanistically unique to Tvacs. Whereas Tinf split their functions between 2 different cell types and either divide
or become memory, Tvacs do both within the same cell. Our data support an entirely novel model of CD8+ T
cell activation whereby two transcription factors normally opposed to one another in function instead cooperate
to sustain Tvacs exponential clonal expansion as well as a memory cell fate. The goals of this project will be to
understand how these transcription factors cooperate instead of competing to support a vaccine-elicited T cell's
transcriptional and metabolic needs.

## Key facts

- **NIH application ID:** 10812837
- **Project number:** 2R01AI066121-16A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ross M Kedl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,469
- **Award type:** 2
- **Project period:** 2007-01-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812837

## Citation

> US National Institutes of Health, RePORTER application 10812837, Transcriptional and metabolic regulation of vaccine-elicited CD8+ T cell responses (2R01AI066121-16A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10812837. Licensed CC0.

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