# Bispecific and Trispecific Anti-Env Antibodies for Eliminating HIV Reservoir Cells

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $713,872

## Abstract

PROJECT SUMMARY/ABSTRACT
Antibodies constitute a powerful weapon to fight viral infections. They could neutralize the infectivity of virus
particles as well as mediate killing of productively infected cells via mechanisms such as antibody-dependent
cell-mediated cytotoxicity (ADCC). In the past five years, our group has utilized the advances made in the
antibody engineering field, as well as the growing lists of broadly neutralization antibodies (bNAbs) identified by
other investigators, to construct new bispecific antibodies that have exquisite antiviral breadth and potency for
the purpose of HIV-1 prevention. Now, with this proposal, we wish to expand our antibody engineering effort to
generate a collection of bispecific and trispecific antibodies that are optimized for killing of Env-expressing
cells, and for important properties such as pharmacokinetics. Instead of screening for virus-neutralization
activity as we have previously done, we will now engineer and screen a library of Env-targeting multi-specific
antibodies for cell-binding and cell-killing activities in vitro. The best performing antibody constructs will then
be evaluated systematically in vivo in a humanized mouse model for the effect on their cell-killing capacity,
their ability to restrict or eliminate latent reservoir cells after activation, and their ability to prevent or limit the
establishment of the HIV-1 latent reservoir. Along with our knowledge of HIV-1 bNAbs and antibody
engineering, our deep understanding of viral dynamics and our prior experience studying the HIV-1 latent
reservoir will be brought to bear on the design, conduct, and interpretation of experiments to evaluate and
quantify the antiviral effects of our top antibody constructs in humanized mice.
Our group has successfully engineered two bispecific antibodies with exquisite HIV-1-neutralizing activity, and
we have since extended our know-how in antibody engineering to the construction of bispecific or trispecific
antibodies that target Env for the purpose of facilitating the elimination of infected cells. In the end, we hope to
offer to the field one or two multi-specific antibodies that could be applied toward the elimination of latent
reservoir cells as one critical component of a multi-pronged approach to HIV-1 eradication.

## Key facts

- **NIH application ID:** 10224769
- **Project number:** 5R01AI129802-06
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID D HO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $713,872
- **Award type:** 5
- **Project period:** 2017-07-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224769

## Citation

> US National Institutes of Health, RePORTER application 10224769, Bispecific and Trispecific Anti-Env Antibodies for Eliminating HIV Reservoir Cells (5R01AI129802-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10224769. Licensed CC0.

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