# Project 1 - Development of mRNA Immunogens for Protective Antibody Induction

> **NIH NIH U19** · DUKE UNIVERSITY · 2022 · $2,197,512

## Abstract

Vaccine trials in non-human primates challenged with R5, tier 2 SHIVs have shown protection in the
presence of high levels of non-neutralizing antibodies (NNAbs), and one of the 5 Phase IIb HIV-1 vaccine
efficacy trials using alum (ALVAC/AIDSVAX in RV144) showed an estimated vaccine efficacy of 31%, with a
correlate of decreased transmission risk of V2 and other FcR-mediated anti-HIV antibodies. NNAbs are
polyfunctional antibodies capable of mediating a number of FcR-mediated or complement-mediated functions
such as ADCC, antibody dependent cellular phagocytosis (ADCP) or NK cytokine production. A new efficacy
trial is ongoing to follow-up on RV144, called HVTN702, using ALVAC-C, a bivalent clade C gp120 boost, and
the adjuvant MF59. We have demonstrated that a multivalent wildtype (WT) Env ALVAC/protein vaccine
protected macaques by ~55% from robust (12 intrarectal challenges) challenge with R5, tier 2 SHIV. In this
study, the immune correlates of protection were NNAbs that mediated infected cell antibody binding, ADCC,
ADCP of challenge SHIV and MIP1β expression by NK cells. The overall hypothesis of project 1 is that the
efficacy of RV144 and the current HVTN 702 efficacy trial will be improved upon by use of mRNAs encoding
trivalent ADCC mosaic Envs that are specifically designed to overcome NNAb epitope diversity. This will be
accomplished by the following Specific Aims:
Specific Aim 1. Design and produce multivalent nucleoside-modified mRNAs encoding either
polyvalent WT or ADCC mosaic Env gp120s.
Specific Aim 2. Determine the induction of NNAbs induced by trivalent ADCC mosaic vs. WT Envs in
bnAb VH + VL UCA knock-in (KI) mice that express the RV144-derived V2 ADCC-mediating antibody,
CH58.
Specific Aim 3. Test ALVAC-C/trivalent ADCC Env gp120s in rhesus macaques (RMs) for ability to
protect against an R5, tier 2 transmitted/founder SHIV for use in a phase I clinical trial in year 5.

## Key facts

- **NIH application ID:** 10355428
- **Project number:** 5U19AI142596-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Barton F. Haynes
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,197,512
- **Award type:** 5
- **Project period:** 2019-01-11 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355428

## Citation

> US National Institutes of Health, RePORTER application 10355428, Project 1 - Development of mRNA Immunogens for Protective Antibody Induction (5U19AI142596-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10355428. Licensed CC0.

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