# Manufacture a protein encoding CAP256.wk34.c80 OPT4 envelope for induction of V2 Apex bnAbs

> **NIH NIH UM1** · DUKE UNIVERSITY · 2024 · $5,303,216

## Abstract

Request to DAIDS to Manufacture a protein encoding CAP256.wk34.c80 OPT4 envelope for induction of
V2 Apex bnAbs
Induction of an effective HIV-1 vaccine is a global priority; yet, no HIV-1 vaccine regimen reproducibly elicits
broadly neutralizing antibodies (bnAbs) in humans. The complex immunology underlying human bnAb
development suggests that a successful vaccine will likely contain a series of immunogens that guide bnAb
development 1-3. Such complex vaccines will require iterative design and evaluation in humans, necessitating
rapid cGMP production of potent immunogens. We and others have found that multimerizing HIV-1 Env on
nanoparticles (NPs) can augment its immunogenicity. HIV-1 Env trimer NP immunogens have been made
previously by encoding HIV-1 Env fused to NP subunits as a single gene. These fusion protein NPs display a
mixture of high-quality and low-quality, misfolded HIV-1 Env on their surfaces that can elicit immunodominant
non-neutralizing antibodies. Thus, laborious, time-consuming development work must be performed to
optimize the HIV-1 envelope production such that predominately well-folded envelope is fused to nanoparticle
subunits. Additionally, we have found during cGMP cell line development that protein yields of Env trimer NP
may be insufficient to enable cGMP manufacturing. The significance of this Project is that it will utilize an
already successful cGMP process to rapidly manufacture higher quality HIV-1 Env trimer NPs than previous
NPs encoded by single genes. We have already utilized this technology to overcome the pitfalls incurred with
fusion NPs, by using our innovative conjugation method that generates NPs with only well-folded HIV-1 Env on
their surface. This method utilizes the high specificity of sortase A conjugation to link highly purified, well-folded
HIV-1 Env to ferritin NPs. These sortase A-conjugated NPs (scNPs) can be assembled rapidly and preserve
the antigenic character of the HIV-1 Env, features critical for a vaccine regimen aiming to elicit durable,
protective bnAbs. This innovative, rapid NP platform is universal in nature, having been used for HIV-1 Env
trimers of various clades, SIVcpz Env trimers, and Spike proteins from other human pathogens such as SARS-
CoV-2. We will utilize this platform in combination with CAP256w34.80 designed to guide affinity maturation of
V2 Apex bnAbs in humans.

## Key facts

- **NIH application ID:** 11078959
- **Project number:** 3UM1AI144371-06S5
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Barton F. Haynes
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $5,303,216
- **Award type:** 3
- **Project period:** 2019-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11078959

## Citation

> US National Institutes of Health, RePORTER application 11078959, Manufacture a protein encoding CAP256.wk34.c80 OPT4 envelope for induction of V2 Apex bnAbs (3UM1AI144371-06S5). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11078959. Licensed CC0.

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