# Project 2 - GMP Manufacturing of mRNA Immunogens

> **NIH NIH U19** · DUKE UNIVERSITY · 2022 · $6,432,773

## Abstract

HIV vaccine candidates entering into clinical testing generally fall into three categories: 1) recombinant
envelope (Env) protein immunogens, 2) viral vectors, and 3) plasmid DNA. Numerous vaccine Env designs
are being tested in clinical trials. Likewise, numerous HIV vaccine inserts, such as mosaic sequences, have
been designed to induce broad, protective T-cell responses. However, to date, no specific vaccine regimen
has been able to initiate and expand broadly neutralizing antibody (bnAb) lineages in non-human primates or
humans, nor have induced durable antibody responses. Furthermore, the current platforms have multiple
challenges; the manufacturing processing for sequential protein vaccines may be complex and time-
consuming, viral vectors may have potential pitfalls of anti-vector immunity, and plasmid DNA may have the
need for complex delivery systems to enhance immunogenicity. These potential hurdles highlight the need for
a next generation vaccine platform that possesses favorable production, safety, and immunogenicity
characteristics such as nucleoside-modified messenger (m) RNAs in lipid nanoparticles (LNPs).
 To execute this project, we will select CDMO partners to manufacture two non-neutralizing
antibody(NNAb)-inducing gp120 mRNA immunogens (ADCC Mosaic or WT Env) chosen in overall Aim 1 for
use in a Phase I clinical trial that will start at the mid- to end of year 5 of this grant. By leveraging the existing
expertise for this novel platform, we will accelerate the timeline for evaluating a vaccine in the clinic. The scope
of this work will span knowledge transfer to the selected CDMO through successful IND filing for the final
vaccine candidate. A technical CDMO management team, including CDMO project leaders and Haynes,
Weissman, Maughan and Denny will be assembled to oversee the process and ensure successful delivery of
the program. The following specific aims are proposed for the project.
 • Aim 1. Transfer pre-production knowledge and processes for mRNA immunogens to contract
 development and manufacturing organizations (CDMOs).
 • Aim 2. Deliver final drug substances and drug products for toxicology studies and clinical testing.
 • Aim 3. Develop and deliver regulatory strategies to enable Phase I proof of concept clinical
studies.

## Key facts

- **NIH application ID:** 10355429
- **Project number:** 5U19AI142596-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Thomas Denny
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $6,432,773
- **Award type:** 5
- **Project period:** 2019-01-11 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355429

## Citation

> US National Institutes of Health, RePORTER application 10355429, Project 2 - GMP Manufacturing of mRNA Immunogens (5U19AI142596-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10355429. Licensed CC0.

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