# HIV-1 Env immunogens that target unmutated common ancestor antibodies (UCAs)  of broadly neutralizing antibodies (bnAbs) reactive with multiple HIV-1 envelope epitopes

> **NIH NIH UM1** · DUKE UNIVERSITY · 2024 · $809,741

## Abstract

HIV-1 Env immunogens that target unmutated common ancestor antibodies (UCAs) of broadly neutralizing
antibodies (bnAbs) reactive with multiple HIV-1 envelope epitopes
Current efforts at HIV vaccine development are targeted at devising sequential vaccination regimens that are intended to
mimic the antigenic diversity of the HIV-1 Envelope (Env) as it co-evolves in response to the humoral immune system.1, 2
Sequential vaccination strategies are predicated on the existence of individual envelope immunogens that are capable of
first engaging broadly neutralizing antibody (bnAb) precursors called unmutated common ancestors (UCAs). UCA-
targeting Envs are designed to stimulate a particular class of bnAb precursor to proliferate and develop into a bnAb.1
BnAb precursors can be difficult to stimulate via vaccination due to their low frequency within the human B cell repertoire.1
Recently, progress has been made demonstrating proof of concept of UCA or germline-targeting of individual bnAb B cell
lineages.1 Specifically, germline targeting Envs have been developed for single bnAb B cell lineages targeting either the
HIV Env CD4 binding site, the V3-glycan bnAb Env site, the V2 apex bnAb Env site, the fusion peptide or the membrane
proximal external region (MPER) Env proximal site (reviewed in 1). However, an effective HIV vaccine will need to target
most of these sites simultaneously to escape of transmitted/founder (TF) viruses that initiate infection. Thus, the overall
goal of this supplement is to design a single priming immunogen that can effectively induce bnAb precursors targeting the
V3-glycan, the CD4bs, the V2 apex, and the proximal and distal MPER. Here, we propose to develop a single universal
priming immunogen that can simultaneously initiate multiple B cell clonal lineages against multiple bnAb-antigenic sites,
thereby both simplifying HIV vaccine design, and improving the probability of inducing rare bnAb precursors bnAb B cell
lineages for which precursors of individual B cell lineages are extremely rare.1

## Key facts

- **NIH application ID:** 11078956
- **Project number:** 3UM1AI144371-06S2
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Barton F. Haynes
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $809,741
- **Award type:** 3
- **Project period:** 2019-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11078956

## Citation

> US National Institutes of Health, RePORTER application 11078956, HIV-1 Env immunogens that target unmutated common ancestor antibodies (UCAs)  of broadly neutralizing antibodies (bnAbs) reactive with multiple HIV-1 envelope epitopes (3UM1AI144371-06S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11078956. Licensed CC0.

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