# Optimization of Broadly Neutralizing Antibodies for HIV Eradication

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $696,167

## Abstract

SUMMARY
One of the current leading HIV cure approaches is the “shock and kill” strategy. This approach takes into
account that virus reactivation alone will not likely lead to eradication of the reservoir, and that an additional
immunologic effector mechanism will almost certainly be required to eliminate reactivated cells. While cytotoxic
T cells have frequently been proposed as potential killers that may be recruited for such a strategy, broadly
neutralizing antibodies (bNAbs) can also induce rapid destruction of target cells by directing the
cytotoxic and antiviral activity of the innate immune system. This has been widely exploited by the
monoclonal antibody therapeutics community in developing improved antibodies for cancer but has not yet
been explored for HIV.
Antibody Fc-engineering efforts have modified antibodies to ensure that they are able to drive killing of the
targets, and not only bind them. Point mutations have been introduced to selectively and specifically drive
relevant effector functions, bi- and tetra-specific antibodies have been engineered to broaden and optimize
targeting, and natural Fc-optimization strategies via glycan engineering have been utilized to collectively tune
and promote more effective Fc-effector function for target cell elimination. In this proposal, we hypothesize
that rational antibody engineering will result in functional optimization of bNAbs that will more
effectively eliminate the viral reservoir for HIV eradication.
Specific Aim 1: Design and down-select a panel of Fc point mutants and/or glycan variants that drive
reservoir clearance.
Specific Aim 2: Develop a bi- or tetra-specific antibody that drives reservoir eradication.
Specific Aim 3: Evaluate the efficacy of the optimized bNAbs for virus eradication in ART-suppressed,
SHIV-infected rhesus monkeys.

## Key facts

- **NIH application ID:** 9970401
- **Project number:** 5R01AI129797-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Galit Alter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $696,167
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970401

## Citation

> US National Institutes of Health, RePORTER application 9970401, Optimization of Broadly Neutralizing Antibodies for HIV Eradication (5R01AI129797-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970401. Licensed CC0.

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