# Optimization of Fc effector activity of anti-HIV antibodies to target HIV reservoir

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $847,498

## Abstract

ABSTRACT
A major barrier to HIV cure is the persistence of HIV-1-infected cells that constitute the HIV reservoir. Although
current antiretroviral pharmacologic strategies have no impact on the elimination of the HIV reservoir, anti-HIV-
1 antibodies can specifically target these cells through Fc effector activity, suggesting their potential clinical use
for the control of HIV-1 infection. In several pre-clinical evaluation studies, administration of broadly
neutralizing anti-HIV-1 antibodies (bNAbs) provided both effective pre-exposure prophylaxis and durable
suppression of virus replication in chronically infected models of in vivo HIV-1 infection. More importantly,
recent evaluation of the protective activity of these bNAbs in HIV-1-infected patients revealed the capacity of
these bNAbs to confer viremic control, as evidenced by the reduction in plasma viremia following bNAb
administration. Interactions of the Fc domain of bNAbs with FcγRs expressed on the surface of effector
leukocytes contribute to their in vivo antiviral activity by inducing opsonization and clearance of viral particles
as well as elimination of HIV-infected cells. Given the importance of Fc effector activity of bNAbs to induce
clearance of HIV-infected cells, the proposed studies aim to develop and characterize Fc-optimized bNAbs
with improved Fc effector function. The activity of these bNAbs will be evaluated in vitro in well-established
cytotoxicity assays, and in vivo in humanized mouse models of HIV-1 infection, as well as in SHIV-infected
rhesus monkeys. Fc-optimized bNAbs for enhanced effector activity are expected to specifically target HIV-
infected cells, providing sustained disease control and augmented therapeutic potential compared to
conventional bNAbs.

## Key facts

- **NIH application ID:** 9962279
- **Project number:** 5R01AI129795-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Michel C Nussenzweig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $847,498
- **Award type:** 5
- **Project period:** 2017-08-05 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962279

## Citation

> US National Institutes of Health, RePORTER application 9962279, Optimization of Fc effector activity of anti-HIV antibodies to target HIV reservoir (5R01AI129795-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9962279. Licensed CC0.

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