# Messenger RNA immunogens for initiation of HIV V3-glycan neutralizing B cell lineages

> **NIH NIH U19** · DUKE UNIVERSITY · 2020 · $4,527,376

## Abstract

A key goal of HIV-1 vaccine development is to induce long-lasting broadly neutralizing antibodies (bnAbs)
that can inhibit HIV-1 infection. Messenger (m) RNA has emerged as a promising new vaccine modality that
can elicit potent immune responses, while avoiding the safety risks and anti-vector immunity associated with
some live virus vaccines. Important targets for bnAb induction are N301, N332 glycans at the base of the
gp120 V3 loop. Our overall goals in this grant are 1) To design an mRNA that encodes a V3-glycan
mimetope that, when expressed, will bind a V3 glycan UCA; 2) To select and produce mRNA formulations
non-GMP that encode HIV-1 Envs for immunization in humanized mice and RMs; and 3) To produce the
sequential V3-glycan mRNA vaccine under CGMP conditions, perform toxicity studies, and prepare an IND for
testing in a Phase I trial in man.
Overall Specific Aim 1. Develop mRNA delivery constructs for sequential Env trimers for V3-glycan
bnAb B cell lineage vaccinations.
Hypotheses: Messenger RNA vaccination of humanized mice, Rhesus macaques and humans will induce
long-lasting anti-V3 glycan bnAb epitope antibodies, and mRNA vaccination will promote sequential somatic
hypermutations and affinity maturation in V3-glycan targeted B cell lineages.
Overall Specific Aim 2. Produce CGMP mRNA immunogens.
Hypotheses: Messenger RNAs can be produced and encapsulated in potent nanoparticle formulations under
CGMP for use in human Phase I trials, and will be safe and immunogenic. Moreover, the mRNA immunogens
selected for CGMP production will produce stable Env trimers upon transfection of cell lines in vitro and after
immunization in vivo in humanized mice.
Expectations and Impact on the Field. Messenger RNAs are the current most promising vaccine strategy for
inducing high-titered and long-lasting antibody responses. A successful first in man Phase I clinical trial with
clinical trials materials produced in this IPCAVD will change the field by showing the plausibility of initiation of
V3-glycan bnAb B cell lineages.

## Key facts

- **NIH application ID:** 9868256
- **Project number:** 5U19AI135902-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Barton F. Haynes
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,527,376
- **Award type:** 5
- **Project period:** 2018-02-08 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868256

## Citation

> US National Institutes of Health, RePORTER application 9868256, Messenger RNA immunogens for initiation of HIV V3-glycan neutralizing B cell lineages (5U19AI135902-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9868256. Licensed CC0.

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