# Project 1: Establishing a robust functional cure

> **NIH NIH U19** · BOSTON CHILDREN'S HOSPITAL · 2024 · $1,698,874

## Abstract

PROJECT SUMMARY (Project 1 – Robust functional cures with AAV-expressed eCD4-Ig) 
eCD4-Ig is a potent and exceptionally broad fusion of the first two domains of CD4 to an antibody Fc 
domain and a short tyrosine-sulfated coreceptor-mimetic peptide. In rhesus macaques, adeno-associated 
virus (AAV)-expressed eCD4-Ig mediates consistent and very effective protection against SHIV-AD8 and 
SIVmac239. eCD4-Ig also has properties that make it especially useful for establishing a functional cure in 
rhesus macaques and perhaps in humans. These include its potency, breadth, difficulty-of-escape, low 
immunogenicity when expressed by AAV, consistent expression by AAV, potent intrinsic ADCC activity, and 
collaboration with serum antibodies to mediate ADCC. These properties allow eCD4-Ig to circumvent two 
major problems associated with using AAV-expressed antibodies to establish functional cures, namely 
immune clearance and viral escape. In preliminary data we show that AAV-expressed eCD4-Ig can 
suppress replication of SHIV-AD8 for more than a year in 5 of 6 macaques. However we also show that, 
when compared to the “Monkey monkey” described in Project 2, this suppression was less robust, meaning 
that consistent ‘blipping’ of virus was observed in most eCD4-Ig-suppressed animals. Because the Miami 
monkey expresses roughly 10 times the amount of total antibody observed in these eCD4-Ig-expressing 
macaques, we hypothesize that greater expression of eCD4-Ig will result in more robust functional cures. 
The goals of this project are thus to increase AAV-mediated expression of eCD4-Ig, to establish robust 
functional cures in SHIV-AD8 and SIVmac239-infected macaques, to amplify the ADCC activities in these 
macaques by stimulating host antibody responses to epitopes unmasked by eCD4-Ig, to establish a 
consistent platform that will allow for evaluation of latency reversing agents, and to ask whether long-term 
expression of eCD4-Ig by itself can impact the viral reservoir. These studies will improve and help 
understand a viable approach to establishing similar functional cures in humans.

## Key facts

- **NIH application ID:** 10864932
- **Project number:** 5U19AI149646-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Mauricio A Martins
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,698,874
- **Award type:** 5
- **Project period:** 2020-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864932

## Citation

> US National Institutes of Health, RePORTER application 10864932, Project 1: Establishing a robust functional cure (5U19AI149646-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10864932. Licensed CC0.

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