# Molecular and cellular basis of Combined Adjuvant-Elicited Cellular Immunity

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $481,682

## Abstract

Project Summary
Immunization with antigen in the presence of agonists for both a Toll Like Receptor
(TLR) and CD40 (combined TLR/CD40 immunization) elicits a vigorous expansion of
antigen-specific CD8+ T cells that is exponentially greater than the response elicited by
either agonist alone. Not only is the primary immune response to this vaccination robust,
it also forms long lived, CD8+ T cell memory that can protect against future infectious
challenge even in the absence of CD4+ T cells. This has been recently verified in non-
human primates, where the vaccine produced responses exponentially stronger than
responses to typical viral vectors. Given the potency and clinical potential for this
vaccine adjuvant platform, it is critical that we understand its molecular and cellular
mechanistic underpinnings. We recently made the surprising discovery that T cell
responses to this, and related, vaccinations were unexpectedly and completely
dependent on two cytokines (IL-27 and IL-15) and two transcription factors (Tbet and
Eomes). This was unexpected because the loss of any one of these factors essentially
ablates the response to the vaccine but has little to no effect on the response to live
virus or bacteria. Thus, the rules behind robust subunit vaccine-elicited immunity appear
to be substantially different than those guiding infectious responses. This proposal will
use cutting edge methods and approaches to fully understand the nature of this
difference and will test i) how IL-27 and IL-15 influence downstream transcriptional and
cellular factors, ii) how Tbet and Eomes expression subsequently program T cell
activation and expansion, and iii) how these factors mediate T-DC and T-T interactions
during the earliest events of T cell activation after combined adjuvant vaccination.

## Key facts

- **NIH application ID:** 9952298
- **Project number:** 5R01AI126899-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ross M Kedl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $481,682
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952298

## Citation

> US National Institutes of Health, RePORTER application 9952298, Molecular and cellular basis of Combined Adjuvant-Elicited Cellular Immunity (5R01AI126899-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9952298. Licensed CC0.

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