# AAV-mediated delivery of eCD4-Ig for prevention and treatment of perinatal HIV infection

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $825,106

## Abstract

PROJECT SUMMARY
 Mother-to-child transmission of human immunodeficiency virus (HIV) still results in hundreds of
thousands of new pediatric HIV infections every year, especially in resource-poor areas of the world where
access to antenatal/postnatal antiretroviral therapy (ART) is limited. Sadly, in the absence of ART, >50% of HIV-
infected infants die by 2 years of age. Since ART alone will not be sufficient to end the morbidity and mortality
associated with HIV/AIDS in children, there is an urgent need for developing practical interventions to prevent
and treat pediatric HIV infection. To that end, this project will evaluate the potential of gene therapy with the
potent and extremely broad HIV inhibitor eCD4-Ig to prevent and treat perinatal HIV infection. eCD4-Ig is a
chimeric molecule consisting of the outer domains of CD4, an IgG Fc portion, and a co-receptor mimetic peptide.
eCD4-Ig has unmatched breadth and very potent effector activities against HIV-1, HIV-2, and SIV. The eCD4-Ig
gene will be delivered to infant rhesus macaques (RMs) via adeno-associated virus (AAV)-mediated gene
transfer. AAV vectors are safe and can transduce both dividing and non-dividing cells. Critically, AAV-driven
transgene expression in long-lived cells, such as those of skeletal muscle, can last for years, possibly decades.
While AAV-mediated delivery of eCD4-Ig has been shown to protect adult RMs against challenge with pathogenic
immunodeficiency viruses bearing highly divergent Envelope proteins, this approach has never been tested in
infants. We have recently partnered with the Farzan lab to characterize the kinetics of eCD4-Ig expression in
infant RMs treated with AAV/eCD4-Ig at birth. Compared to adult animals, AAV/eCD4-Ig-treated newborn RMs
experienced substantially higher levels of eCD4-Ig and lower levels of antibodies against the eCD4-Ig molecule.
Note that these anti-drug antibodies (ADAs) are highly detrimental to AAV-mediated delivery of immunoglobulins
because they can clear the molecules from circulation, thereby reducing the efficacy of this approach. The low
levels of ADAs observed in the AAV/eCD4-Ig-treated infants is consistent with previous reports of neonates
developing tolerance to AAV-delivered transgene products. Given the ability of AAV vectors to promote sustained
transgene expression after a one-time administration, and the unique window of opportunity offered by the
neonatal period to achieve robust AAV-driven expression of eCD4-Ig in vivo, we postulate that AAV-mediated
delivery of eCD4-Ig to infants can prevent and treat postpartum HIV infection. In specific aim (SA) 1, we will
characterize the safety profile of AAV/eCD4-Ig in infant RMs. In SA 2, we will determine if neonatal delivery of
AAV/eCD4-Ig can prevent oral acquisition of SIVmac239 in RMs. In SA 3, we will assess if AAV-mediated
delivery of eCD4-Ig to SIV-infected infant RMs can control viral replication without ART. If successful, the
proposed experiments will build the pr...

## Key facts

- **NIH application ID:** 10692877
- **Project number:** 5R01HD102252-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Mauricio A Martins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $825,106
- **Award type:** 5
- **Project period:** 2020-08-07 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692877

## Citation

> US National Institutes of Health, RePORTER application 10692877, AAV-mediated delivery of eCD4-Ig for prevention and treatment of perinatal HIV infection (5R01HD102252-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692877. Licensed CC0.

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