# HIV-1 Fusion Peptide-directed Vaccine Design Using Virus-like Particles

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $923,921

## Abstract

PROJECT SUMMARY
There is an unmet need in the HIV vaccine field for immunogens that consistently elicit potent serum antibodies
that neutralize a broad spectrum of HIV-1 variants in circulation worldwide. Recently, we identified a novel target
for human neutralizing antibodies (NAbs): the eight N-terminal amino acids of the fusion peptide (FP) on
prefusion HIV-1 envelope (Env) trimer (Science 2016). We then created a novel immunization strategy: priming
with FP conjugated to the carrier protein keyhole limpet hemocyanin (FP-KLH) and boosting with HIV-1 Env
trimer. This strategy has reproducibly elicited FP-directed cross-reactive NAbs in multiple studies involving mice,
guinea pigs and non-human primates (NHPs), although not in every animal (Nat Med 2018, Cell 2019). The best
monoclonal antibody (mAb) from an immunized NHP neutralized 98% of 58 wild-type HIV-1 strains with FP
sequence matching the immunogen, and 59% of 208 strains that represent viruses worldwide and contain
diverse FP sequences. Therefore, FP prime/Env boost is a promising strategy for eliciting NAb responses. To
further improve FP-directed vaccine design, two main limitations need to be addressed. First, the neutralization
breadth of the polyclonal sera from immunized animal is still limited. Second, the cross-neutralizing activities
were only observed in a small subset of immunized animals and were generally low-titer. To address these
limitations, in this proposal, we will develop novel FP immunogens and immunization strategies to improve the
breadth (Aim 1), magnitude (Aim 2) and quality (Aim 3) of the FP-directed responses in guinea pigs and non-
human primates.

## Key facts

- **NIH application ID:** 10257205
- **Project number:** 1R01AI162267-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rui Kong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $923,921
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10257205

## Citation

> US National Institutes of Health, RePORTER application 10257205, HIV-1 Fusion Peptide-directed Vaccine Design Using Virus-like Particles (1R01AI162267-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10257205. Licensed CC0.

---

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