# Discovery of Novel Epitopes for Antibody Dependent Cell-mediated Cytotoxicity Against HIV-1 Infected Cells

> **NIH NIH R21** · EMORY UNIVERSITY · 2021 · $223,125

## Abstract

Project Summary/Abstract
HIV research efforts are strongly focused on developing vaccines that can elicit highly protective antibody
responses. There is evidence from human and nonhuman vaccine studies that both neutralizing and non-
neutralizing antibody activities contribute to protection against acquisition. Importantly, the only phase III vaccine
efficacy trial to show a signal of protection in human volunteers demonstrated that antibody dependent cell-
mediated cytotoxicity (ADCC) was associated with reduced acquisition, compelling us to know more about this
Fc-mediated antiviral function. We previously recovered a unique collection of more than 300 monoclonal
antibodies from 6 recently HIV-1 infected individuals from Zambia and Rwanda and found that a subset of these
antibodies mediated ADCC against target cells coated with the envelope gp120 protein from the autologous,
transmitted/founder (T/F) variant. This activity was associated with antibodies that had shorter CDRH3 regions
and lower neutralization activity against the T/F envelope pseudovirus than antibodies lacking ADCC activity.
Modeling and competition studies suggested that some of the ADCC-mediating antibodies recognize novel
epitopes. Here, we will test these monoclonal antibodies for ADCC against target cells infected with the authentic
T/F variant created by molecular cloning, and compare the results with ADCC against target cells coated with
the T/F gp120 protein and neutralization of the T/F Env, the latter being the hallmark of antibody binding to the
functional, virion-associated envelope spike. By using a large number of autologous T/F envelope-antibody
combinations, where the envelope presents the exact epitope or a very close approximation to that which the
antibody was selected against, and two widely used ADCC assays, our studies have the potential to reveal
previously unappreciated mechanistic features of ADCC and identify novel epitopes that can be further
developed and explored for vaccines.

## Key facts

- **NIH application ID:** 10113530
- **Project number:** 5R21AI150292-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Cynthia Ann Derdeyn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,125
- **Award type:** 5
- **Project period:** 2020-02-24 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113530

## Citation

> US National Institutes of Health, RePORTER application 10113530, Discovery of Novel Epitopes for Antibody Dependent Cell-mediated Cytotoxicity Against HIV-1 Infected Cells (5R21AI150292-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10113530. Licensed CC0.

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