# mRNA encoding of immune receptor-targeting antibodies for the augmentation of vaccine-elicited cellular immunity.

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2023 · $194,375

## Abstract

Project summary.
Clinically relevant cellular responses to either experimental or FDA approved vaccine adjuvant formulations
have been difficult to generate and/or detect. We have long been investigating a combined adjuvant
formulation (composed of a TLR agonist and an agonistic antiCD40 antibody) which generates cellular
immunity on par with that observed to infectious challenge. The complexity of this three-part vaccine (antigen
plus TLR/CD40) is limiting to its clinical application. However, the success of lipid nanoparticle (LNP)
encapsulated mRNA vaccines for Covid provides a possible avenue by which our combination adjuvant might
be successfully translated into clinical use against chronic infectious diseases and cancer. Our preliminary
results show that we can agonize the CD40 pathway, sufficient to augment CD8 T cell responses, by mRNA-
mediated delivery of the heavy and light chains of the agonistic anti-CD40 antibody FGK45. The success of
this method for targeting CD40 strongly favors the hypothesis that antibodies specific for other
immunotherapeutic molecular targets (eg. CTLA4, PD1) might also be successfully delivered via the mRNA
vaccination strategy. Completion of this project would not only identify a new and powerful means by which
the established potency of our combined adjuvant might be leveraged for clinical application, they open an
entirely new paradigm in the use of mRNA vaccination for targeting immunologically relevant molecules for the
purposes oncologic checkpoint therapy and beyond.

## Key facts

- **NIH application ID:** 10662571
- **Project number:** 5R21AI171061-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ross M Kedl
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2022-07-08 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662571

## Citation

> US National Institutes of Health, RePORTER application 10662571, mRNA encoding of immune receptor-targeting antibodies for the augmentation of vaccine-elicited cellular immunity. (5R21AI171061-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10662571. Licensed CC0.

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