# Manufacture an mRNA/LNP encoding an HIV envelope designed to bind and stimulate multiple V2 Apex broadly neutralizing antibody B cell lineages

> **NIH NIH UM1** · DUKE UNIVERSITY · 2024 · $3,192,992

## Abstract

Supplement request to DAIDS to Manufacture an mRNA/LNP encoding an HIV envelope
designed to bind and stimulate multiple V2 Apex broadly neutralizing antibody B cell
lineages
Barton Haynes, CHAVD PI
Thomas Denny, Investigator, manufacture team
This request is to produce GMP an mRNA immunogen that encodes an Env that binds to multiple
V2 apex broadly neutralizing antibody (bnAb) naïve B cell precursors that are required for the
acquisition of bnAb breadth against the V2 apex of HIV-1. This mRNA encodes a gp150
immunogen (OPT4.R189T “shielded”) targeting 6 V2 apex UCAs and will be tested both as a
prime and as an immunofocusing boost for induction of V2 apex bnAbs. The immunogen that this
mRNA will be compared with as a prime is a similar protein, OPT4 “unshielded” Env-ferritin
nanoparticle (NP), that targets 9 V2 apex UCAs. Moreover, since the mRNA OPT4.R189T
“shielded” Env can boost on-track V2 apex bnAbs in monkeys, it will be tested as a boosting
immunogen with the protein prime, OPT4 “unshielded” Env-ferritin nanoparticle (NP), that is also
requested to be manufactured in a separate CHAVD manufacturing supplement request. What
follows below is the rationale for requesting the production of the OPT4.R189T “shielded” Env
gp150 mRNA/LNP under GMP conditions in this Y6 CHAVD supplement.
Specific Aim 1. Demonstration batch production and analytical development of candidate
mRNAs.
Specific Aim 2. Deliver final drug substances and drug products for toxicology studies and
clinical testing
Specific Aim 3. Develop and deliver a regulatory strategy to enable Phase I proof of
concept clinical studies.

## Key facts

- **NIH application ID:** 11078951
- **Project number:** 3UM1AI144371-06S4
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Barton F. Haynes
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,192,992
- **Award type:** 3
- **Project period:** 2019-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11078951

## Citation

> US National Institutes of Health, RePORTER application 11078951, Manufacture an mRNA/LNP encoding an HIV envelope designed to bind and stimulate multiple V2 Apex broadly neutralizing antibody B cell lineages (3UM1AI144371-06S4). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11078951. Licensed CC0.

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