# Lymph node-targeted delivery of HIV vaccine candidates

> **NIH NIH F30** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $28,863

## Abstract

PROJECT SUMMARY/ABSTRACT
There is a critical need for a preventative vaccine against human immunodeficiency virus (HIV). Despite
continued structural refinement, immunization with soluble HIV envelope glycoprotein (Env) trimer has yet to
elicit the desired broadly neutralizing antibodies (bNabs). This delay may in part be due to the inefficient delivery
of Env trimer to the follicles of secondary lymphoid organs. The heavy glycosylation of Env, poor complement
fixation, and instability in sera all contribute to inefficient trafficking. Previous work to array Env trimer on the
surface of liposomes has revealed improved antibody responses following immunization. Here we seek to target
Env-displaying liposomes to relevant cell populations native to the lymph node follicle with the goal of increased
neutralizing antibody production. We hypothesize that improved targeting of Env trimer to the lymph node will
bias the antibody repertoire towards neutralizing phenotypes.
This will be accomplished by targeting liposome-bound Env trimer to the two cell populations directing germinal
center (GC) B cell affinity maturation. First, the antigen reservoir of follicular dendritic cells will be targeted,
allowing for continual exposure of GC B cells to neutralizing epitopes. During natural infection, sustained antigen
presentation to GC B cells has been shown to stimulate somatic hypermutation, affinity maturation, and the
development of unusually long heavy chain complementary determining region 3 (HCDR3), characteristic of
bNabs. Second, antigen-specific cognate T follicular helper (Tfh) cell populations will be increased by targeting
immunogen to CLEC9A+XCR1+ dendritic cells, responsible for activating Tfh cells. Previous work has shown that
a large Tfh cell population may reduce competition between neutralizing and non-neutralizing epitope-specific B
cells, favoring the development of neutralizing antibodies. Aim 1 focuses on the delivery of intact Env trimer to
the follicular dendritic cell antigen reservoir, while Aim 2 looks to target delivery to CLEC9A+XCR1+ dendritic cells
with the goal of expanding the antigen specific Tfh cell population. The final Aim looks to characterize the Tfh
and B cell response to immunization with each targeting approach alone and in combination. If successful, this
work will provide a flexible platform for targeted antigen delivery capable of boosting neutralizing antibody
production against HIV.
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## Key facts

- **NIH application ID:** 10011559
- **Project number:** 5F30AI136646-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Geraldine Goebrecht
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,863
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-07-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011559

## Citation

> US National Institutes of Health, RePORTER application 10011559, Lymph node-targeted delivery of HIV vaccine candidates (5F30AI136646-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10011559. Licensed CC0.

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