# Eliciting neutralizing antibodies and B cell responses using novel HIV Env immunogens in non-human primates

> **NIH NIH P01** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $976,445

## Abstract

PROJECT SUMMARY
A broadly effective HIV vaccine remains a high priority to reduce the spread of this highly pathogenic virus in the
human population. Neutralizing antibodies, broadly cross-neutralizing are highly likely needed to be generated
from evolving vaccine candidate immunogens, either protein-based or mRNA-based. Recently, we have elicited
cross-neutralizing serum and serum IgG responses in all macaques immunized with a series of 4 recombinant
highly stable and homogeneous NFL trimers arrayed at high density on fully synthetic trimer-liposomes. Besides
serum cross-neutralization we now have compelling EMPEM apex densities (Ozorowski/Ward – HIVRAD
Structural Core C) to heterologous near-native protein trimers derived from tier 2 viruses not in the immunogen
series. In addition, we know have isolated monoclonal antibodies that possess long and tip-charged HCDR3s
that compete with PGT145 and VRC26 for trimer-binding. These data indicate that these neutralizing antibodies
are likely apex-directed, cross-neutralizing antibodies – a very significant accomplishment for the field. To launch
this study, we initially tested a set of NFL trimers available from the Wyatt lab for recognition by the germline-
reverted NHP bNAb RHA1 from George Shaw (Roark et al, Science 2021). Remarkably, the Q23 NFL displayed
detectable binding that was enhanced by multi-valent array on covalent trimer-liposomes. Accordingly, we used
Q23 NFL trimers and Q23 trimer-liposome (high-valency array) in SMNP adjuvant (Darrell Irvine) to elicit
autologous neutralization. We followed the Q23 NFL prime with heterologous boosting of trimers that are the
most sensitive to apex-directed bNAbs (ie, ZM233, see below). Using this prime:boost strategy we elicited
neutralization of multiple clinical isolates, including the well-studied CH505 transmitter/founder virus. At this
juncture, our initial apex-targeting vaccine experiment in NHPs appears to be quite successful. We have elicited
both autologous Q23, ZM233 and 1428 neutralization, as well as cross-neutralization of tier 2 isolates not in
the vaccine regimen. Accordingly, here, we propose to perform heterologous protection studies of the NFL-
trimer vaccinated NHPs by repetitive low-dose mucosal challenge with the well-characterized, clinical isolate,
transmitter-founder-based CH505 SHIV.

## Key facts

- **NIH application ID:** 11095685
- **Project number:** 3P01AI157299-04S1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Richard Thomas Wyatt
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $976,445
- **Award type:** 3
- **Project period:** 2021-02-04 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11095685

## Citation

> US National Institutes of Health, RePORTER application 11095685, Eliciting neutralizing antibodies and B cell responses using novel HIV Env immunogens in non-human primates (3P01AI157299-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11095685. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*