# An injectable hydrogel platform for sustained release of eCD4-Ig

> **NIH NIH R01** · SCRIPPS FLORIDA · 2020 · $874,862

## Abstract

PROJECT SUMMARY
Combined anti-retroviral therapy (cART) and pre-exposure prophylaxis (PrEP) represent major
milestones in the effort to eliminate AIDS and prevent new HIV-1 infections. They nonetheless have
limitations. For example, a life-time use of two or three compounds delivered to most every cell and
tissue in the body will likely come with undesirable, difficult-to-anticipate side effects. Access and
compliance also remain concerns, especially among infected persons who have not yet been reached
by our healthcare infrastructures. Similarly, PrEP requires both access and a conscious effort before a
potential transmission event, something that is not always realistic for the hardest-to-reach
demographics here and abroad. Here we will develop an approach that provides robust prophylaxis and
perhaps effective viral suppression for six months or more after a single injection. Specifically we will
optimize eCD4-Ig, a very broad and potent antibody-like molecule, for its delivery in an injectable
hydrogel, and we will optimize this hydrogel for delivery of eCD4-Ig. eCD4-Ig provides highly effective
protection in rhesus macaques from high-dose challenges with both SHIV-AD8 and SIVmac239. It also
has the breadth and potency to suppress an established SHIV-AD8 infection. This breadth appears
sufficient to suppress the wide diversity of viruses in an individual and in a population. As importantly,
HIV-1 has not developed easily accessible pathways of escape from eCD4-Ig as it has from neutralizing
antibodies. It is therefore an ideal payload for a safe, effective, and sustained hydrogel delivery system.
As we show, these hydrogels are well-tolerated, non-immunogenic, easily manufactured, and
deliverable with a high-gauge need. Importantly, they and their payloads can be immediately withdrawn
in case of an adverse event. Modeling suggest that they can sustain eCD4-Ig concentrations that could
provide effective prophylaxis for well over six months. We will test this possibility in human FcRn-
transgenic mice and in rhesus macaques, and confirm that our best eCD4-Ig/hydrogel formulations could
replace PrEP and/or cART.

## Key facts

- **NIH application ID:** 10079645
- **Project number:** 1R01AI154989-01
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Eric Andrew Appel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $874,862
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079645

## Citation

> US National Institutes of Health, RePORTER application 10079645, An injectable hydrogel platform for sustained release of eCD4-Ig (1R01AI154989-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10079645. Licensed CC0.

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