# Understanding reservoir effects and curative potential of a CD3/CCR5 bispecific antibody in infant macaques

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $710,095

## Abstract

The goal of this project is to understand reservoir effects and curative potential of a promising
CCR5-depleting bispecific antibody (bsAb) given with days of ART initiation to infants with either
limited or robust pre-ART viral replication. The agent is a bsAb with one arm directed against CD3 and
the other against CCR5, which approximates cytotoxic T cells to CCR5-expressing cells. These cells form a
key part of the HIV reservoir in ART-treated people and have been eliminated in notable cases of HIV cure.
Our preclinical studies revealed >50% remission in simian immunodeficiency virus (SIV)-infected infant
animals after bsAb treatment. We hypothesize that these effects were achieved through a combination of
true reservoir depletion and removal of SIV target cells required for rebound.
In this R01 application, we propose to improve the manufacturing and safety of this bispecific antibody and
then rigorously test the two proposed mechanisms of action. We will screen early-infected infants to identify
those with either (i) limited viral replication and the potential for cure, or (ii) robust replication and likelihood
of establishing measurable reservoirs that can be followed during and after bsAb treatment. These two
groups will be separately studied in order to isolate and measure reservoir effects and the potential for cure.
Hypothesis: Highly purified CD3/CCR5 bsAb, given within days of ART initiation, safely achieves significant
SIV reservoir depletion from infants, which is sufficient to induce durable remission in those with restricted
reservoirs or can act synergistically with bnAb to achieve remission in animals with larger reservoirs.
Aim 1. Test CCR5 depletion and side effects caused by CD3/CCR5 bsAb produced as a CrossMab,
compared to controlled Fab-arm exchange (cFAE).
Aim 2. Demonstrate the potential for infant SIV cure via CCR5 depletion near the time of ART
initiation, when viral replication and reservoirs are limited.
Aim 3. Measure the interference with reservoir establishment that is achievable by CCR5 depletion,
bnAb, or the two combined in early-treated infants with robust viral replication.

## Key facts

- **NIH application ID:** 11022874
- **Project number:** 1R01AI184418-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** DENNIS J. HARTIGAN-O'CONNOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $710,095
- **Award type:** 1
- **Project period:** 2024-08-06 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11022874

## Citation

> US National Institutes of Health, RePORTER application 11022874, Understanding reservoir effects and curative potential of a CD3/CCR5 bispecific antibody in infant macaques (1R01AI184418-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11022874. Licensed CC0.

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