# A safety switch for an effective HIV-1 vaccine

> **NIH NIH DP1** · SCRIPPS FLORIDA · 2021 · $960,000

## Abstract

PROJECT SUMMARY
We have developed what appears to be an effective way to prevent HIV-1 infection despite high-dose
intravenous challenges. This approach combines eCD4-Ig, an exceptionally broad and potent HIV-1
entry inhibitor with an adeno-associated virus (AAV) delivery system. After a one-time intramuscular
inoculation with AAV-eCD4-Ig, rhesus macaques were protected for more than a year from multiple
high-dose challenges with SHIV-AD8 and SIVmac239. This protection is likely to last for several
additional years or more. A similar approach might also be taken using a cocktail of AAV-expressed
broadly neutralizing antibodies (bNAbs), presuming that the problem of their greater immunogenicity
can be addressed. In short, we are close to providing effective, long term protection for high-risk
individuals such as intravenous drug users. However, there is one clear hurdle remaining. Specifically,
while it is likely that eCD4-Ig and bNAbs are safe when passively administered, these proteins have
never been expressed in many people for long periods of time, and there is no easy remedy for an
adverse event. To that end, we are intensively exploring ways to suppress or stop entirely expression
of an AAV transgene. We propose here to develop a number of small on- and off-switches that
modulate transgene message-RNA stability, as well as kill-switches that permanently halt transgene
expression. Our focus is on switches that are practical for in vivo use, always keeping our eye on the
larger goal of making an effective HIV-1 prophylaxis strategy safe.

## Key facts

- **NIH application ID:** 10114261
- **Project number:** 5DP1DA043912-05
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Michael R. Farzan
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $960,000
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114261

## Citation

> US National Institutes of Health, RePORTER application 10114261, A safety switch for an effective HIV-1 vaccine (5DP1DA043912-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114261. Licensed CC0.

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