# Using monoclonal antibody Fc variants in strategies to eliminate HIV reservoirs

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $838,801

## Abstract

PROJECT SUMMARY
New approaches for curative treatments could substantially reduce the numbers of individuals living with HIV-
1, thus diminishing the need for life-long adherence to ART. However, solutions must include clearing infection
and preventing latent reservoirs. While ART is the standard of care for HIV+ individuals, the field has not yet
addressed an alternative to ART therapy that could halt infection and halt virus expansion. A proven nonhuman
primate (NHP) model for infection that examines new therapeutic regimens that can be instituted very soon
after virus exposure, or in cases of viral control under ART, is needed to address whether it is possible to
eradicate HIV. With the discoveries of extremely potent and broad antibodies that target multiple determinants
on the HIV-1 Envelope, a cure strategy is now recognized as an attainable goal. The overall goal of this project
is to design Fc function-enhanced anti-HIV-1 human monoclonal antibodies (mAbs) and test them for virus
eradication in rhesus macaques in a Clade C, Tier 2, SHIV post-exposure protection model. Anti-viral functions
mediated by the Fc part of the molecule are crucial to antibody protection against HIV, but clearing HIV-1
infection using antibodies is a new paradigm for antibodies. Specific combinations of neutralizing mAbs have
been predicted to have the potential for neutralization coverage against large cross-clade panels of HIV-1
isolates; V2-directed mAbs were identified as an immune correlate of RV144 in reducing infection risk. Our
working hypothesis is that combinations of mAbs, if enhanced for antibody-dependent cellular cytotoxicity
(ADCC), phagocytosis (ADCP), and complement activation, and engineered and tested in vivo for increased
half-life, would be extremely effective in ablating early acute infection and limiting or eliminating seeding of viral
reservoirs. The project proposal outlines a research plan to engineer, develop and characterize in vitro a panel
of human monoclonal anti-HIV mAbs with enhanced effector function designed to increase the effectiveness of
killing HIV-1 infected cells. Fc regions of mAbs of known potency and breadth will be modified by site directed
mutagenesis for increased effector functions and for optimal affinity to human and macaque FcRs. Once
modified, functional assays will be used to evaluate the improvements in ADCC, ADCP and complement
activation. Increased half-life evaluations will be performed in NHP. Combinations of modified mAbs will be
tested in vitro to identify the most optimal groupings for additive effect of neutralization and effector functions.
These mAbs will be chosen for large-scale production in amounts and purity needed for macaque experiments.
An iterative progression of post-infection studies will be conducted in rhesus macaques, testing several
combinations and examining doses and varying intervals before treatment. The practical goal is to formulate
the most optimal combinations of mAbs that prov...

## Key facts

- **NIH application ID:** 9970191
- **Project number:** 5R01AI129801-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Ann Jones Hessell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $838,801
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970191

## Citation

> US National Institutes of Health, RePORTER application 9970191, Using monoclonal antibody Fc variants in strategies to eliminate HIV reservoirs (5R01AI129801-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9970191. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*